How long does stem cell therapy take to work in clinical trials?

In the randomized knee osteoarthritis trials, pain scores separated from control from the third month onward in a 2024 meta-analysis of 16 trials with 875 patients [2]. At one year, 19 of 26 outcome measures favored the cells across 14 trials in a 2021 review, with low to very low certainty [1]. Those are study observations, and any plan for a patient is set by the practitioner.

How long do stem cells last after injection?

Labeled cells infused by vein in four patients had fallen from about 30 percent in the lungs to 2 to 5 percent by day 10 [9]. In an autopsy study, donor DNA was found after 9 of 13 infusions given within 50 days but after only 2 of 8 given earlier, at 1 in 100 to below 1 in 1,000 of cells [11]. In mice, viable cells were recoverable for 24 hours [13].

How many sessions did the stem cell trials use?

The published trials mostly used a single intra-articular session. One 26-patient randomized trial compared one session with sessions at baseline and six months and reported a WOMAC pain score of 1.1 in the two-session group against 4.3 with hyaluronic acid at 12 months [7]. A 30-patient trial found no difference between 10 million and 100 million cells over four years [6].

What do joint injection studies report after a stem cell injection?

Iijima and colleagues pooled 35 studies with 2,385 patients and reported knee pain or swelling after injection at 2 to 60 percent, with no severe events [3]. Wiggers and colleagues reported no serious adverse events over up to four years across 14 randomized trials [1]. Symptom scores in those trials changed over months [2].

What is the stem cell results timeline in the trials?

Pooled pain scores separated from control from month 3 [2]. At 12 months, trials report lower pain and higher function scores, with MRI measures unchanged [1, 4, 7]. At four years, the one randomized trial with that follow-up reported median pain of 2 to 3 in the cell groups against 7 in control, in 30 patients [6].

Do stem cells stay in the body?

The evidence says mostly no. Tracking studies in people show lung retention within minutes of an intravenous infusion and clearance over hours to days, with signal moving to liver and spleen [9, 10]. Autopsy data show donor DNA at 1 in 100 to below 1 in 1,000 of cells, falling with time, and no ectopic tissue [11]. Researchers propose the effect runs through the recipient’s immune cells [15, 16].

Do stem cells go to the lungs after an IV infusion?

Yes, as a first pass. Fischer and colleagues showed in rats that most MSCs were trapped in the lungs after intravenous infusion [14]. In four patients, 27 to 33.5 percent of labeled activity sat in the lungs immediately after infusion and 2 to 5.4 percent by day 10 [9]. A 2021 review of 109 studies reported the same lung-first pattern across species [8].

How long have trials followed stem cell therapy results?

The longest randomized follow-up with outcome scores is four years, in 30 patients, where median pain stayed at 2 to 3 in the cell groups against 7 in control [6]. A 2021 review found no serious adverse events over a maximum of four years across 14 trials [1]. Beyond that point the registered trial literature has not yet reported.

What does the FDA state about stem cell products for knee pain?

The FDA consumer alert states that none of the products it lists have been approved for any orthopedic condition, including osteoarthritis and knee pain, and that the approved stem cell products are cord blood derived blood-forming cells [21]; the current FDA list also includes OMISIRGE and several gene-modified hematopoietic stem cell products [25]. The one approved MSC product, from December 2024, is for a pediatric transplant complication [23].

Does freezing change stem cells?

Moll and colleagues reported in 2014 that freeze-thawed MSCs showed reduced responsiveness to inflammatory stimuli, stronger complement activation and faster lysis after serum exposure than fresh cells, and that patients given fresh low-passage cells responded at 100 percent against 50 percent for thawed higher-passage cells [20]. Post-thaw viability and passage number therefore appear on a documented lot record.

6 November 2026 · Updated November 2026 · 15 min read

How Long Does Stem Cell Therapy Take to Work? Timelines From Investigational Trials and Tracking Studies

How long does stem cell therapy take to work? The follow-up visits knee trials measured, out to 4 years, and how fast labeled cells cleared in tracking studies.

Stem CellsMesenchymal Stem CellsTimelineBiodistributionKnee Osteoarthritis TrialsParacrine HypothesisFDAPatient Guides

Benn Bluestein-Veyra, M.Sc. Organic Chemistry | ExaVeyra Sciences

Cited sources

In the randomized knee osteoarthritis trials where most human outcome data outside transplantation exist, pain scores separated from control from the third month onward in a 2024 meta-analysis of 16 trials with 875 patients, and 19 of 26 outcome measures favored mesenchymal stem cells at one year in a 2021 review of 14 trials [1, 2]. Tracking studies show the infused cells themselves clear within days to weeks, so any timeline describes a response the body makes after most of the cells are gone [9, 11].

Five threads answer the timing question: the follow-up points registered trials and meta-analyses actually measured, how long labeled cells were detectable in people and in animals, the mechanism proposed to reconcile the two, the product variables that change what reaches a patient, and the questions the evidence has left open. The article is written for patients and practitioners who want the sources behind the timelines quoted online. ExaVeyra Sciences supplies mesenchymal stem cells from an FDA-registered tissue bank, and any plan for a patient is set by the practitioner.

randomized knee trials with 875 patients in the 2024 meta-analysis whose follow-up schedule the first section reads

10 days

after intravenous infusion, labeled cell signal in the lungs of four patients had fallen from about 30 percent to 2 to 5 percent in the 2011 tracking study

4 years

longest follow-up with reported pain and function scores in a 30-patient randomized knee trial published in 2018

Regulatory status

The FDA states in its consumer alert that stem cell products generally require FDA approval, that the approved stem cell products consist of blood-forming stem cells derived from umbilical cord blood, and that none of the products it lists have been approved for any orthopedic condition, including osteoarthritis and knee pain [21]. The agency’s current approved-products list also includes OMISIRGE, made from cord blood, and several gene-modified hematopoietic stem cell products [25], and one mesenchymal stromal cell product has been approved, in December 2024, for a pediatric transplant complication [23]. Most other MSC products are section 351 biologics that reach a patient through a biologics license or an investigational new drug application [24]. ExaVeyra supplies mesenchymal stem cells from an FDA-registered tissue bank to practices in states whose laws permit it, with the 351 biologic status applying everywhere, and the practitioner and their counsel decide whether and how any product is used.

Registered trials measure outcomes at 3, 6, 12 and 24 months

The timeline people search for is a set of follow-up visits in a trial protocol. Xie and colleagues pooled 16 randomized trials with 875 knee osteoarthritis patients in 2024 and reported that pain scores separated from control from the third month onward, with no difference from control on whole-organ MRI scores [2].

Wiggers and colleagues reviewed 14 randomized trials of autologous MSCs in 408 patients in 2021 and reported that at one year 19 of 26 clinical outcome measures improved compared with control, with pain lower by 1.8 to 4.4 points on a 0 to 10 scale and KOOS higher by 18 to 32 points [1]. Four of those trials showed better imaging at one year, and the authors graded the certainty of the whole body of evidence as low to very low [1].

Source	Design and size	Follow-up points reported	Main finding at those points
Xie 2024 [2]	16 randomized trials, 875 patients	Monthly to 12 months in pooled analysis	Pain scores lower than control from month 3 onward; MRI scores unchanged
Wiggers 2021 [1]	14 randomized trials, 408 patients	1 year, with a maximum of 4 years	19 of 26 outcome measures improved at 1 year; no serious adverse events
Iijima 2018 [3]	35 studies, 2,385 patients	Study end points, mixed designs	Pain and function improved; limited effect on cartilage volume
Kim 2019 [4]	5 randomized trials, 220 patients	Trial end points to 24 months	Pain and Lysholm favored cells; WOMAC and MRI did not differ
Lamo-Espinosa 2018 [6]	30 patients, randomized phase I/II	12 months, then 4 years	Median pain 2 to 3 in cell groups against 7 in control at 4 years
Matas 2019 [7]	26 patients, randomized phase I/II	6 and 12 months	WOMAC pain 1.1 against 4.3 at 12 months after cells at baseline and month 6

Kim and colleagues pooled the five randomized trials available in 2017, 220 patients, and reported that pain and Lysholm scores favored the cells while WOMAC and MRI measures of cartilage repair did not differ from control [4]. Iijima and colleagues pooled 35 studies with 2,385 patients and reported improved pain and function with a limited effect on cartilage volume, and a better function result where rehabilitation accompanied the cells [3].

Longer follow-up exists in a few small randomized trials

Lamo-Espinosa and colleagues followed the 30 patients of a phase I/II randomized trial for four years and reported in 2018 median pain scores of 2 and 3 in the two cell groups against 7 in the hyaluronic acid control, with WOMAC changes of minus 18 and minus 10 against plus 4, and no adverse effects [6]. The trial compared 10 million and 100 million cultured autologous bone marrow cells and found no difference between them [6].

Matas and colleagues randomized 26 patients to hyaluronic acid, 20 million umbilical cord MSCs once, or the same cell number at baseline and at six months, and reported at 12 months a WOMAC pain score of 1.1 in the two-session group against 4.3 with hyaluronic acid, with no MRI differences and no severe adverse events [7]. Several authors hold positions at the cell manufacturer, which the paper discloses [7].

Xiao and colleagues pooled the three randomized trials of umbilical cord MSCs available in 2024 and reported a WOMAC reduction of 25.85 points against control, while noting the small number of studies [5]. Across these trials the symptom scores and the imaging diverge: the reviews report lower pain scores between 3 and 12 months and no difference from control on MRI [2, 4, 7].

Tracking studies show the cells themselves clear within days to weeks

Gholamrezanezhad and colleagues infused indium-labeled bone marrow MSCs by peripheral vein in four patients in 2011 and imaged them to day 10 [9]. Activity appeared first in the lungs at 27 to 33.5 percent, fell to 2 to 5.4 percent by day 10, and rose meanwhile in the liver to 13 to 17.4 percent and in the spleen to 30.1 to 42.2 percent, the picture of cells and cell debris being cleared, with no sign of homing to a target [9].

Sood and colleagues labeled autologous bone marrow cells with FDG in 21 patients in 2015 and found lung retention at 30 minutes after intravenous infusion with significant clearance by 90 minutes and no discernible homing to the target organ, while arterial routes produced retention there [10]. Sanchez-Diaz and colleagues reviewed 109 biodistribution studies in 2021 and reported that the human pattern resembles the animal pattern for each route [8].

The longest human persistence data come from autopsy. Von Bahr and colleagues found donor DNA in 9 of 13 infusions given within 50 days of sampling and in 2 of 8 given earlier, at 1 in 100 to below 1 in 1,000 of cells, with no correlation between detection and response [11]. In mice, viable donor cells were recoverable from the lungs for 24 hours and from no other organ, after a first pass in which most cells were trapped in the pulmonary capillaries [13, 14].

The paracrine hypothesis proposes how an effect can outlast the cells

If the cells are gone in days while the trial scores move over months, researchers have proposed that something other than engraftment carries the effect [15, 16, 17]. Caplan, who coined the term, proposed in 2017 that the cells be renamed medicinal signaling cells because in the body they act by secreting factors at sites of injury rather than by engrafting and differentiating [17].

Galleu and colleagues showed in 2017 that recipient cytotoxic cells induce infused MSCs to undergo apoptosis, that recipient phagocytes then produce indoleamine 2,3-dioxygenase, and that among patients only those with high cytotoxic activity against MSCs responded [15]. De Witte and colleagues tracked human umbilical cord MSCs in mice in 2018 and found most of them dead within 24 hours and contained in monocytes, which changed phenotype and traveled to other sites [16].

Galipeau and Sensébé reviewed the clinical record in 2018 and placed the inconsistent results on heterogeneity between products, donors and manufacturing, short persistence, and the gap between preclinical and clinical potency [18]. On that reading, the timeline is a property of the recipient’s response to a particular product, which is why trials report it per product and per follow-up point.

Understanding what the evidence does not yet show

The trials answer when outcome measures were taken and what they showed for the product each trial used. Several questions a patient naturally asks remain unanswered by that literature.

How long a symptom change lasts beyond four years, the longest randomized follow-up with outcome scores, in a trial of 30 patients [6]
Whether one session or several produce a different course, tested in a single 26-patient trial with 12 months of follow-up [7]
Whether a structural change on imaging follows the symptom change, since pooled MRI measures did not differ from control [2, 4]
How the course differs between bone marrow, adipose and umbilical cord products, which the meta-analyses compare only indirectly [2, 3]
What the course looks like for routes other than intra-articular injection, where human outcome data in registered trials are far thinner [12]
How post-thaw viability and passage number at the point of use change the response, since most products reach a practice frozen [20]

Thawing, passage and cell number change what reaches the patient

Levy and colleagues counted more than 1,050 registered clinical trials exploring MSCs in 2020 and noted that most clinical-stage programs had been unable to meet their primary efficacy end points, with heterogeneity introduced at each manufacturing step as a leading explanation [19]. Thompson and colleagues, pooling 55 randomized trials, asked future trials to report MSC characterization more fully for the same reason [12].

Moll and colleagues compared freeze-thawed with freshly harvested MSCs in 2014 and reported reduced responsiveness to inflammatory stimuli, stronger complement activation and faster lysis after serum exposure in the thawed cells, and a 100 percent response rate in patients given fresh low-passage cells against 50 percent for thawed higher-passage cells in a comparable group [20]. Post-thaw viability and passage number therefore belong on any lot record a practice reads.

The approved MSC product illustrates how a timeline is written into a protocol. The FDA release for Ryoncil describes a 54-patient single-arm study in which eight infusions were given over four consecutive weeks and response was assessed 28 days after the first, with complete response in 30 percent and partial response in 41 percent [23]. The timing was fixed by the protocol and measured at a fixed point, the same way every timeline in this article was measured.

The knee trials read their outcomes at fixed visits, the tracking studies follow labeled cells for hours to days, and the proposed link between the two runs through the recipient’s own immune cells.

The timeline is a study observation and the practitioner sets any plan

Every figure in this article is a follow-up point in a trial or a measurement in a tracking study, specific to the product, the cell number and the route that study used. ExaVeyra supplies mesenchymal stem cells from an FDA-registered tissue bank that ships to all 50 states and Puerto Rico, with a lot number on every vial and a certificate of analysis for every lot, with serology; the characterization panel, including post-thaw viability and passage number, and the cold-chain records are available on request.

Whether a product is used, for whom, by which route and on what schedule is a decision for the practitioner and their counsel under state law. Florida, Georgia, Tennessee, Nevada and Utah have enacted permission statutes with conditions on supplier accreditation, written notice and consent, Texas and North Carolina make selling adult stem cells for investigational use a crime, and the state guides on this site set out each statute with its primary source. The FDA patient page adds that listing on clinicaltrials.gov or registration with FDA does not mean a product is legally marketed, and that the agency has repeatedly notified clinics of the need for an IND [22].

A verified account gives a practice the lot data behind any timeline

The route forward for a practice is a verified account. Anyone may apply or ask the scientific team a question without an NPI, and NPI verification, which takes 1 to 3 business days, gives access to the practitioner portal, product documentation and pricing. From the portal a practice can request the certificate of analysis, the characterization panel and the cold-chain records for a lot before anything is ordered.

Patients can ask a practice for the same documents and for the follow-up points the practice itself records, and the FDA consumer alert invites questions by phone and email about any product offered [21]. A practice that reads its lot records against the trial follow-up schedule described here has a defensible basis for its own documentation, and the registered trial literature continues to add follow-up points each year.

Educational Disclaimer: This article is for educational purposes only and does not constitute medical or legal advice. It does not identify any material, compound, device setting or protocol as safe, effective or appropriate for any patient, and it is not intended to diagnose, treat, cure, or prevent any disease. Questions about a treatment belong with the reader’s own licensed provider. Exosome material is supplied for topical aesthetic use by licensed practitioners. No exosome product is FDA-approved for any use, and ExaVeyra Sciences makes no statement about administration, route, or outcome. Compounded medications are not FDA-approved. They are prepared by a 503A compounding pharmacy licensed by the Texas State Board of Pharmacy for an individual patient against that patient’s prescription, and are available to NPI-verified licensed practitioners only, in the states where the pharmacy is licensed. Product, device and brand names mentioned are trademarks of their respective owners and are used only to identify the products discussed. Their mention is not an endorsement, and those owners have not reviewed or endorsed this article. ExaVeyra Sciences is a supplier and takes no part in any diagnosis, treatment decision, or plan of care. Findings described are attributed to the peer-reviewed literature, trial registries and agencies cited. The content of these guides is provided for general informational purposes only. It does not constitute legal, medical, or regulatory advice, and does not establish that any particular product or practice is compliant. Regulatory requirements vary by state and depend on the circumstances of each practice. Each practitioner should consult their own legal counsel and the applicable state licensing boards before acting on anything stated here.

References

1.Wiggers TG, Winters M, Van den Boom NA, Haisma HJ, Moen MH. Autologous stem cell therapy in knee osteoarthritis: a systematic review of randomised controlled trials. Br J Sports Med. 2021;55(20):1161-1169. PMID 34039582. doi:10.1136/bjsports-2020-103671Systematic review of randomized controlled trials of autologous MSCs from bone marrow, adipose tissue or activated peripheral blood in knee osteoarthritis, searches to December 2020, with ROB 2 and GRADE; 14 trials, 408 patients. Carries in this article: at 1 year, 19 of 26 clinical outcome measures (73 percent) improved with MSCs compared with control, pain fell by 1.8 to 4.4 points on a 0 to 10 scale and KOOS rose by 18 to 32 points, four trials showed better imaging at 1 year, follow-up reached a maximum of 4 years, and certainty was low to very low. Disclosure: competing interests none declared.
2.Xie RH, Gong SG, Song J, Wu PP, Hu WL. Effect of mesenchymal stromal cells transplantation on the outcomes of patients with knee osteoarthritis: A systematic review and meta-analysis. J Orthop Res. 2024;42(4):753-768. PMID 37991925. doi:10.1002/jor.25724Meta-analysis of randomized controlled trials of MSCs from different tissue sources in knee osteoarthritis; 16 studies, 875 patients. Carries in this article: pain scores separated from control from the third month onward, subgroups by source and by autologous or allogeneic origin differed, and whole-organ MRI scores did not differ from control. Disclosure: none stated in the PubMed record.
3.Iijima H, Isho T, Kuroki H, Takahashi M, Aoyama T. Effectiveness of mesenchymal stem cells for treating patients with knee osteoarthritis: a meta-analysis toward the establishment of effective regenerative rehabilitation. NPJ Regen Med. 2018;3:15. PMID 30245848. doi:10.1038/s41536-018-0041-8Systematic review with meta-analysis and meta-regression; 35 studies, 2,385 patients, mean ages 36 to 74.5 years. Carries in this article: pooled standardized mean differences of minus 1.45 for pain and 1.50 for self-reported function, a limited effect on cartilage volume, minor adverse events (knee pain or swelling) at 2 to 60 percent with no severe events, very low to low GRADE certainty, and a better function result where rehabilitation accompanied the cells. Disclosure: no competing financial interests.
4.Kim SH, Ha CW, Park YB, Nam E, Lee JE, Lee HJ. Intra-articular injection of mesenchymal stem cells for clinical outcomes and cartilage repair in osteoarthritis of the knee: a meta-analysis of randomized controlled trials. Arch Orthop Trauma Surg. 2019;139(7):971-980. PMID 30756165. doi:10.1007/s00402-019-03140-8Meta-analysis of randomized controlled trials, searches to March 2017; 5 trials, 220 patients, two at low risk of bias. Carries in this article: pooled pain scores (mean difference minus 9.2 on a 100-point scale) and Lysholm scores (plus 8.7) favored MSCs while WOMAC did not reach significance, and MRI measures of cartilage repair did not differ from control. Disclosure: none stated in the PubMed record.
5.Xiao Z, Wang X, Li C, Luo L, Li W. Effects of the umbilical cord mesenchymal stem cells in the treatment of knee osteoarthritis: A systematic review and meta-analysis. Medicine (Baltimore). 2024;103(46):e40490. PMID 39560593. doi:10.1097/MD.0000000000040490Meta-analysis restricted to umbilical cord derived MSCs, searches to March 2024; 3 randomized trials. Carries in this article: WOMAC fell by a mean difference of 25.85 points and Lysholm rose by 18.33 points compared with control, with the authors noting that the number of included studies was small. Disclosure: no conflicts of interest.
6.Lamo-Espinosa JM, Mora G, Blanco JF, Granero-Moltó F, Núñez-Córdoba JM, López-Elío S, et al. Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: long-term follow up of a multicenter randomized controlled clinical trial (phase I/II). J Transl Med. 2018;16(1):213. PMID 30064455. doi:10.1186/s12967-018-1591-7Four-year follow-up of a phase I/II multicenter randomized trial (NCT02123368) in 30 knee osteoarthritis patients, comparing hyaluronic acid alone with hyaluronic acid plus 10 million or 100 million cultured autologous bone marrow MSCs. Carries in this article: median pain scores at 4 years of 7 in the control group against 2 and 3 in the cell groups, WOMAC changes of plus 4 against minus 18 and minus 10, no adverse effects reported, and no difference between the two cell numbers. Funding: non-US government support.
7.Matas J, Orrego M, Amenabar D, Infante C, Tapia-Limonchi R, Cadiz MI, et al. Umbilical Cord-Derived Mesenchymal Stromal Cells (MSCs) for Knee Osteoarthritis: Repeated MSC Dosing Is Superior to a Single MSC Dose and to Hyaluronic Acid in a Controlled Randomized Phase I/II Trial. Stem Cells Transl Med. 2019;8(3):215-224. PMID 30592390. doi:10.1002/sctm.18-0053Phase I/II randomized trial (NCT02580695) in 26 knee osteoarthritis patients: hyaluronic acid at baseline and 6 months, 20 million umbilical cord MSCs once, or the same cell number at baseline and 6 months, followed for 12 months. Carries in this article: WOMAC pain at 12 months of 1.1 in the two-session group against 4.3 with hyaluronic acid, no MRI differences, and no severe adverse events. Disclosure: several authors hold employment or leadership positions at Cells for Cells, the cell manufacturer.
8.Sanchez-Diaz M, Quiñones-Vico MI, Sanabria de la Torre R, Montero-Vílchez T, Sierra-Sánchez A, Molina-Leyva A, et al. Biodistribution of Mesenchymal Stromal Cells after Administration in Animal Models and Humans: A Systematic Review. J Clin Med. 2021;10(13):2925. PMID 34210026. doi:10.3390/jcm10132925Systematic review of biodistribution studies across intravenous, intra-arterial, intramuscular, intra-articular and intralesional routes; 109 articles. Carries in this article: the intravenous route produces an initial accumulation in the lungs with later redistribution to liver, spleen and kidneys, the intra-arterial route bypasses the lungs, local routes lack systemic distribution, and the pattern in humans resembles that in animals. Disclosure: no conflict of interest declared.
9.Gholamrezanezhad A, Mirpour S, Bagheri M, Mohamadnejad M, Alimoghaddam K, Abdolahzadeh L, et al. In vivo tracking of 111In-oxine labeled mesenchymal stem cells following infusion in patients with advanced cirrhosis. Nucl Med Biol. 2011;38(7):961-967. PMID 21810549. doi:10.1016/j.nucmedbio.2011.03.008Human tracking study: four patients received 250 to 400 million bone marrow MSCs by peripheral vein, half of them labeled with indium-111 oxine, with whole-body imaging to day 10. Carries in this article: activity appeared first in the lungs and fell from 27 to 33.5 percent to 2 to 5.4 percent by day 10, while liver activity rose to 13 to 17.4 percent and spleen activity to 30.1 to 42.2 percent. Disclosure: none stated in the PubMed record.
10.Sood V, Mittal BR, Bhansali A, Singh B, Khandelwal N, Marwaha N, et al. Biodistribution of 18F-FDG-Labeled Autologous Bone Marrow-Derived Stem Cells in Patients With Type 2 Diabetes Mellitus: Exploring Targeted and Intravenous Routes of Delivery. Clin Nucl Med. 2015;40(9):697-700. PMID 26164170. doi:10.1097/RLU.0000000000000850Human PET tracking study of autologous bone marrow mononuclear cells in 21 patients, seven each by peripheral vein or by two arterial routes, imaged at 30 and 90 minutes. Carries in this article: the intravenous group showed lung retention at 30 minutes with significant clearance by 90 minutes and no discernible homing to the target organ, while arterial routes produced retention there. Disclosure: none stated in the PubMed record.
11.von Bahr L, Batsis I, Moll G, Hägg M, Szakos A, Sundberg B, et al. Analysis of tissues following mesenchymal stromal cell therapy in humans indicates limited long-term engraftment and no ectopic tissue formation. Stem Cells. 2012;30(7):1575-1578. PMID 22553154. doi:10.1002/stem.1118Autopsy study of 18 patients who had received HLA-mismatched MSCs, with 108 tissue samples from 15 patients examined by PCR. Carries in this article: donor DNA was found in 9 of 13 infusions given within 50 days of sampling and in 2 of 8 given earlier, at levels of 1 in 100 to below 1 in 1,000, with no correlation between engraftment and response, which the authors read as a hit-and-run mechanism. Disclosure: none stated in the PubMed record.
12.Thompson M, Mei SHJ, Wolfe D, Champagne J, Fergusson D, Stewart DJ, et al. Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: An updated systematic review and meta-analysis. EClinicalMedicine. 2020;19:100249. PMID 31989101. doi:10.1016/j.eclinm.2019.100249Systematic review and random-effects meta-analysis of randomized controlled trials of intravascular MSCs in adults, searches to May 2018; 55 trials, 2,696 patients. Carries in this article: transient fever was the only event more frequent with MSCs, and the authors call for better reporting of MSC characterization in future trials. Funding: Stem Cell Network, Ontario Institute for Regenerative Medicine and Ontario Research Fund; two authors report affiliations with Northern Therapeutics.
13.Eggenhofer E, Benseler V, Kroemer A, Popp FC, Geissler EK, Schlitt HJ, et al. Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion. Front Immunol. 2012;3:297. PMID 23056000. doi:10.3389/fimmu.2012.00297Mouse tracking study of 500,000 labeled MSCs infused by tail vein, with re-culture of tissues at 5 minutes, 1, 24 and 72 hours. Carries in this article: most label sat in the lungs at 1 hour and in the liver at 24 hours, viable donor MSCs were recovered from the lungs up to 24 hours and from no other organ, and the authors conclude that long-term effects must run through other cell types. Disclosure: none stated in the PubMed record.
14.Fischer UM, Harting MT, Jimenez F, Monzon-Posadas WO, Xue H, Savitz SI, et al. Pulmonary passage is a major obstacle for intravenous stem cell delivery: the pulmonary first-pass effect. Stem Cells Dev. 2009;18(5):683-692. PMID 19099374. doi:10.1089/scd.2008.0253Rat study comparing four cell types infused intravenously with continual arterial sampling and organ imaging. Carries in this article: most MSCs were trapped in the lungs after infusion, smaller cell types passed two- to thirty-fold more readily, and the authors describe the number of MSCs reaching the arterial circulation acutely as therapeutically questionable. Pre-2011 landmark cited in addition to the recent sources.
15.Galleu A, Riffo-Vasquez Y, Trento C, Lomas C, Dolcetti L, Cheung TS, et al. Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation. Sci Transl Med. 2017;9(416):eaam7828. PMID 29141887. doi:10.1126/scitranslmed.aam7828Mouse model of graft-versus-host disease with a parallel analysis of patients who had received MSCs. Carries in this article: recipient cytotoxic cells induce infused MSCs to undergo apoptosis, recipient phagocytes then produce indoleamine 2,3-dioxygenase, and only patients with high cytotoxic activity against MSCs responded, the finding that an effect can follow the death of the infused cells. Disclosure: none stated in the PubMed record.
16.de Witte SFH, Luk F, Sierra Parraga JM, Gargesha M, Merino A, Korevaar SS, et al. Immunomodulation By Therapeutic Mesenchymal Stromal Cells (MSC) Is Triggered Through Phagocytosis of MSC By Monocytic Cells. Stem Cells. 2018;36(4):602-615. PMID 29341339. doi:10.1002/stem.2779Mouse tracking study of viable and dead human umbilical cord MSCs with in vitro monocyte experiments. Carries in this article: viable cells were in the lungs immediately after infusion, most were dead within 24 hours and contained in monocytes in lung and liver, and the monocytes that had taken them up changed phenotype and traveled to other sites, the proposed carrier of an effect after the cells are gone. Disclosure: non-US government support; two authors employed by Orbsen Therapeutics.
17.Caplan AI. Mesenchymal Stem Cells: Time to Change the Name! Stem Cells Transl Med. 2017;6(6):1445-1451. PMID 28452204. doi:10.1002/sctm.17-0051Perspective by the investigator who coined the term. Carries in this article: the proposal to rename the cells medicinal signaling cells, on the ground that in vivo they act by secreting factors at sites of injury in place of engrafting and differentiating, the clearest statement of the paracrine hypothesis. Funding: NIH and non-US government support listed in the PubMed record.
18.Galipeau J, Sensébé L. Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities. Cell Stem Cell. 2018;22(6):824-833. PMID 29859173. doi:10.1016/j.stem.2018.05.004Narrative review. Carries in this article: the summary of why clinical results have been inconsistent, including heterogeneity between products, donors and manufacturing, the short persistence of the cells, and the gap between preclinical and clinical potency, the frame for reading any timeline as product-specific. Disclosure: none stated in the PubMed record.
19.Levy O, Kuai R, Siren EMJ, Bhere D, Milton Y, Nissar N, et al. Shattering barriers toward clinically meaningful MSC therapies. Sci Adv. 2020;6(30):eaba6884. PMID 32832666. doi:10.1126/sciadv.aba6884Narrative review. Carries in this article: more than 1,050 clinical trials exploring MSCs were registered at that time, most clinical-stage MSC programs had been unable to meet primary efficacy end points, and translation is impaired by steps that introduce heterogeneity. Funding: NIH, US non-PHS and non-US government support listed in the PubMed record.
20.Moll G, Alm JJ, Davies LC, von Bahr L, Heldring N, Stenbeck-Funke L, et al. Do cryopreserved mesenchymal stromal cells display impaired immunomodulatory and therapeutic properties? Stem Cells. 2014;32(9):2430-2442. PMID 24805247. doi:10.1002/stem.1729Laboratory comparison of freeze-thawed and freshly harvested MSCs with a retrospective clinical comparison. Carries in this article: thawed cells showed reduced responsiveness to inflammatory stimuli, stronger complement activation and faster lysis after serum exposure, and patients given fresh low-passage cells had a 100 percent response rate against 50 percent for thawed higher-passage cells in a comparable group, the reason post-thaw viability and passage number sit on a lot record. Funding: NIH and non-US government support; no conflicts declared.
21.U.S. Food and Drug Administration. Consumer Alert on Regenerative Medicine Products Including Stem Cells and Exosomes. Dated July 22, 2020; content current as of April 9, 2024; verified 4 November 2026. https://www.fda.gov/vaccines-blood-biologics/consumers-biologics/consumer-alert-regenerative-medicine-products-including-stem-cells-and-exosomesAgency consumer page. Carries in this article: stem cell products generally require FDA approval; the approved stem cell products consist of blood-forming stem cells derived from umbilical cord blood, approved for disorders of blood production; and none of the products the page lists have been approved for any orthopedic condition, including osteoarthritis and knee pain.
22.U.S. Food and Drug Administration. Important Patient and Consumer Information About Regenerative Medicine Therapies. Dated June 3, 2021; verified 4 November 2026. https://www.fda.gov/vaccines-blood-biologics/consumers-biologics/important-patient-and-consumer-information-about-regenerative-medicine-therapiesAgency consumer page. Carries in this article: before approval these products require FDA oversight in a clinical trial, the agency has repeatedly notified clinics of the need for investigational new drug applications, and inclusion in clinicaltrials.gov or registration with FDA does not mean a product is legally marketed.
23.U.S. Food and Drug Administration. FDA Approves First Mesenchymal Stromal Cell Therapy to Treat Steroid-refractory Acute Graft-versus-host Disease. Press release, December 18, 2024; verified 4 November 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-mesenchymal-stromal-cell-therapy-treat-steroid-refractory-acute-graft-versus-hostAgency press release. Carries in this article: Ryoncil (remestemcel-L-rknd) was approved for pediatric patients aged two months and older on the basis of a 54-patient single-arm study in which eight infusions were given over four consecutive weeks and response was assessed 28 days after the first, with complete response in 30 percent and partial response in 41 percent, an example of a timeline written into a protocol and measured at a fixed point.
24.U.S. Food and Drug Administration. 21 CFR 1271.10, Are my HCT/Ps regulated solely under section 361 of the PHS Act and the regulations in this part, and if so what must I do? (66 FR 5466, 2001, as amended 2004; text verified on eCFR 4 November 2026). https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=1271.10 and https://www.ecfr.gov/current/title-21/chapter-I/subchapter-L/part-1271/subpart-A/section-1271.10Federal regulation. Carries in this article: the four cumulative criteria (minimal manipulation, homologous use, no combination with another article beyond the listed agents, and no systemic effect or dependence on living cells unless autologous, close-relative or reproductive) that place a product under section 361 alone, and why culture-expanded allogeneic MSC products fall under section 351.
25.U.S. Food and Drug Administration. Approved Cellular and Gene Therapy Products. Content current as of October 30, 2026; verified 5 November 2026. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-productsAgency list of licensed cellular and gene therapy products. Carries in this article: the list names nine licensed HPC, Cord Blood products, OMISIRGE (a cord blood derived product), gene-modified autologous hematopoietic stem cell products including CASGEVY, ZYNTEGLO, LYFGENIA, SKYSONA and LENMELDY, and RYONCIL, the only licensed MSC product, which updates the 2020 consumer alert sentence on approved stem cell products.

Frequently Asked Questions

How long does stem cell therapy take to work in clinical trials?: In the randomized knee osteoarthritis trials, pain scores separated from control from the third month onward in a 2024 meta-analysis of 16 trials with 875 patients [2]. At one year, 19 of 26 outcome measures favored the cells across 14 trials in a 2021 review, with low to very low certainty [1]. Those are study observations, and any plan for a patient is set by the practitioner.
How long do stem cells last after injection?: Labeled cells infused by vein in four patients had fallen from about 30 percent in the lungs to 2 to 5 percent by day 10 [9]. In an autopsy study, donor DNA was found after 9 of 13 infusions given within 50 days but after only 2 of 8 given earlier, at 1 in 100 to below 1 in 1,000 of cells [11]. In mice, viable cells were recoverable for 24 hours [13].
How many sessions did the stem cell trials use?: The published trials mostly used a single intra-articular session. One 26-patient randomized trial compared one session with sessions at baseline and six months and reported a WOMAC pain score of 1.1 in the two-session group against 4.3 with hyaluronic acid at 12 months [7]. A 30-patient trial found no difference between 10 million and 100 million cells over four years [6].
What do joint injection studies report after a stem cell injection?: Iijima and colleagues pooled 35 studies with 2,385 patients and reported knee pain or swelling after injection at 2 to 60 percent, with no severe events [3]. Wiggers and colleagues reported no serious adverse events over up to four years across 14 randomized trials [1]. Symptom scores in those trials changed over months [2].
What is the stem cell results timeline in the trials?: Pooled pain scores separated from control from month 3 [2]. At 12 months, trials report lower pain and higher function scores, with MRI measures unchanged [1, 4, 7]. At four years, the one randomized trial with that follow-up reported median pain of 2 to 3 in the cell groups against 7 in control, in 30 patients [6].
Do stem cells stay in the body?: The evidence says mostly no. Tracking studies in people show lung retention within minutes of an intravenous infusion and clearance over hours to days, with signal moving to liver and spleen [9, 10]. Autopsy data show donor DNA at 1 in 100 to below 1 in 1,000 of cells, falling with time, and no ectopic tissue [11]. Researchers propose the effect runs through the recipient’s immune cells [15, 16].
Do stem cells go to the lungs after an IV infusion?: Yes, as a first pass. Fischer and colleagues showed in rats that most MSCs were trapped in the lungs after intravenous infusion [14]. In four patients, 27 to 33.5 percent of labeled activity sat in the lungs immediately after infusion and 2 to 5.4 percent by day 10 [9]. A 2021 review of 109 studies reported the same lung-first pattern across species [8].
How long have trials followed stem cell therapy results?: The longest randomized follow-up with outcome scores is four years, in 30 patients, where median pain stayed at 2 to 3 in the cell groups against 7 in control [6]. A 2021 review found no serious adverse events over a maximum of four years across 14 trials [1]. Beyond that point the registered trial literature has not yet reported.
What does the FDA state about stem cell products for knee pain?: The FDA consumer alert states that none of the products it lists have been approved for any orthopedic condition, including osteoarthritis and knee pain, and that the approved stem cell products are cord blood derived blood-forming cells [21]; the current FDA list also includes OMISIRGE and several gene-modified hematopoietic stem cell products [25]. The one approved MSC product, from December 2024, is for a pediatric transplant complication [23].
Does freezing change stem cells?: Moll and colleagues reported in 2014 that freeze-thawed MSCs showed reduced responsiveness to inflammatory stimuli, stronger complement activation and faster lysis after serum exposure than fresh cells, and that patients given fresh low-passage cells responded at 100 percent against 50 percent for thawed higher-passage cells [20]. Post-thaw viability and passage number therefore appear on a documented lot record.

The monthly FDA and state law roundup

One email a month for licensed practices: FDA actions, compounding updates and state law changes that affect what you can source, each with its official source linked.

No spam. Unsubscribe any time.

For Clinics

Apply for Clinic Access

NPI-verified clinic access to our full catalog.

Apply for Clinic Access →

Sourcing Guide

Exosome Sourcing

What to look for: COA, particle count, and quality standards.

Read guide →

Compliance Guide

503A and 503B, Explained

How compounding pharmacies work, and what to ask before you order.

Read guide →

← Back to Resources·All ExaBlog articles →