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MSC Sources: Bone Marrow, Adipose, Umbilical Cord and Placenta

Por Benn Bluestein-Veyra, M.Sc. en Química Orgánica · Actualizado el 20 de octubre de 2026

MSC source tissues include bone marrow, adipose tissue, the umbilical cord with its Wharton’s jelly, and the placenta, and comparative studies show that bone marrow vs adipose vs umbilical cord MSCs differ in colony frequency, growth and differentiation.^[1] Cells from adult and neonatal tissues share core properties while differing in proliferative capacity, surface markers and secreted factors.^[2]

This reference describes how each tissue is obtained, where the cells sit within it, and what side-by-side studies measured. Mattar and Bieback note that relatively few studies compare sources directly, so the comparisons below name the study behind each finding.^[3]

Understanding the shared definition behind every MSC source

Friedenstein and colleagues described fibroblast colonies growing from single adherent cells in monolayer cultures of guinea pig bone marrow, the origin of the colony-forming unit fibroblast (CFU-F) assay.^[4] The CFU-F assay remains the standard measure of progenitor frequency in a fresh tissue sample.^[5]

The International Society for Cellular Therapy (ISCT) set minimal criteria in 2006: plastic adherence, expression of CD105, CD73 and CD90, absence of hematopoietic markers and HLA-DR, and differentiation to osteoblasts, adipocytes and chondroblasts in vitro.^[6] Cells from every tissue on this page are compared against that common panel.^[2]

CD73 is the ecto-5′-nucleotidase encoded by the NT5E gene, a plasma membrane enzyme that converts extracellular nucleotides to nucleosides.^[7] Hass and colleagues describe MSCs as found in nearly all tissues and located mostly in perivascular niches.^[2]

Bone marrow aspirates established the reference MSC population

Pittenger and colleagues isolated MSCs from marrow aspirates of volunteer donors in 1999. The cells kept a stable phenotype as a monolayer, and single cells expanded into colonies that retained adipocytic, chondrocytic and osteocytic potential.^[8]

MSCs are present at low frequency in bone marrow, so they are isolated by expansion in culture. Baxter and colleagues measured telomere shortening during that expansion and reported that even minimal expansion used about half of the cells’ replicative lifespan.^[9]

Ganguly and colleagues aspirated iliac crest marrow from 67 healthy donors aged 19 to 89 and measured MSC number directly by CFU-F assay and by CD45lowCD271+ cell counts. Both methods showed fewer MSCs per milliliter of aspirate with increasing age, with large variation between donors.^[10]

Adipose tissue yields the highest colony frequency among adult sources

Zuk and colleagues isolated processed lipoaspirate cells from human liposuction tissue in 2002. The cells and their clones differentiated along osteogenic, adipogenic, myogenic and chondrogenic lineages and showed a CD marker profile similar to, though distinct from, marrow MSCs.^[11]

Aust and colleagues measured a mean yield of 404,000 adipose-derived cells per milliliter of lipoaspirate across 18 donors. Among the female donors, yield fell as body mass index rose and showed no correlation with donor age.^[12] Kern and colleagues found colony frequency highest in adipose tissue among the sources they compared.^[1]

The stromal vascular fraction precedes the cultured cell

Enzymatic digestion of adipose tissue releases the stromal vascular fraction (SVF), a mixed population. The IFATS and ISCT joint statement identifies SVF stromal cells as CD45−CD235a−CD31−CD34+, with CD13, CD73, CD90 and CD105 adding further detail.^[5]

After culture, adipose-derived stromal cells share CD90, CD73, CD105 and CD44 with other MSCs. The same statement notes that they can be told apart from marrow MSCs by CD36 expression and absent CD106.^[5]

The umbilical cord holds MSCs in distinct anatomical zones

The term human umbilical cord is covered by a single layer of amniotic epithelium that encloses Wharton’s jelly, a mucoid connective tissue around two arteries and one vein (Fig. 1). Davies and colleagues proposed a histological nomenclature for these structures because studies had described the same cells under different anatomical names.^[13]

• Subamniotic zone: Wharton’s jelly just beneath the amniotic epithelium, with a slightly denser matrix and no clefts.^[13]
• Intervascular, or intermediate, Wharton’s jelly: the central tissue between the vessels, crossed by clefts of ground substance.^[13]
• Perivascular zone: a denser band of cells and matrix around each vessel, where CD146-positive cells accumulate during gestation.^[13]

Karahuseyinoglu and colleagues found two cord stromal cell types in culture, distinguished by vimentin and cytokeratin filaments, and matched them to region-specific cells in cord sections. Both types differentiated to chondrogenic, adipogenic and osteogenic lineages.^[14]

Perivascular cells give high colony frequency

Sarugaser and colleagues isolated human umbilical cord perivascular (HUCPV) cells and measured a CFU-F frequency of 1 in 333. Doubling time fell from 60 h at passage 0 to 20 h at passage 2, producing over 10¹⁰ cells within 30 days.^[15]

Baksh and colleagues compared HUCPV cells with bone marrow stromal cells. The cord cells proliferated faster, differentiated to all three lineages, progressed through osteogenesis more rapidly and expressed more CD146.^[16]

Wharton’s jelly gives the largest cell numbers

Subramanian and colleagues compared cells from the amnion, subamnion, perivascular zone, Wharton’s jelly and mixed cord of five cords (Fig. 2). Wharton’s jelly occupied the largest area and gave 4.61 × 10⁶ fresh cells per centimeter of cord without culture.^[17]

Cells from all five compartments proliferated, expressed the typical MSC markers and formed adipocytes, chondrocytes and osteocytes. Cells from Wharton’s jelly showed a stellate epithelioid-like morphology in primary culture, while the other compartments gave short fibroblast-like cells (Fig. 3).^[17]

Placental MSCs come from fetal and maternal layers

The term placenta has a fetal side, made of the amniotic membrane, the chorionic plate and the chorionic villi, and a maternal side, the decidua basalis (Fig. 4). Silini and colleagues describe the chorionic plate as vascularized chorionic mesenchyme from which stem villi branch into the intervillous space.^[18]

The decidua basalis is a thin plate of maternal endometrial tissue that lies between the myometrium and the chorionic plate, and anchoring villi attach to it. Silini and colleagues proposed a shared nomenclature for each perinatal tissue and the cells isolated from it.^[18]

The first international Workshop on Placenta Derived Stem Cells, summarized by Parolini and colleagues in 2008, called for each study to define the region of origin and the isolation method of its placental cells. Most published work had focused on stromal cells from various placental regions and on amniotic epithelial cells.^[19]

Origin testing separates fetal from maternal cells

In ’t Anker and colleagues used HLA typing to show that amnion gives fetal MSCs and decidua basalis and parietalis give maternal MSCs. Phenotypes were comparable, and both placental MSC types expanded more than adult bone marrow MSCs.^[20]

Wu and colleagues confirmed fetal origin for MSCs from the umbilical cord, amniotic membrane and chorionic plate, and maternal origin for decidua parietalis MSCs. Fetal MSCs expanded significantly more than maternal MSCs, and paracrine factor levels differed across sources.^[21]

Sardesai and colleagues found maternal cells in cultures from every chorionic region tested, and maternal cells came to dominate standard-medium cultures started from fetal villi. Focal dissection of the cotyledon core with explant culture in endothelial growth medium selected fetal villous MSCs, which were smaller, more osteogenic and more proliferative.^[22]

Region and donor both matter. Huang and colleagues reported that chorionic plate MSCs kept their fetal origin over serial passages and showed the strongest proliferation and migration among placental MSCs.^[23] Tai and colleagues found stable surface markers across chorionic plate, amniotic and decidual MSCs from five placentas, alongside region- and donor-specific differences in growth and differentiation.^[24]

Perinatal tissues are collected after delivery

The placenta and umbilical cord are delivered at birth, so collecting them requires no procedure on the donor. Parolini and colleagues describe placental tissue as readily available and easily procured without invasive procedures.^[19]

Cord tissue also lends itself to a quick, standardized derivation. Subramanian and colleagues reported that Wharton’s jelly cells can be generated in large numbers with minimal culture.^[17] Bone marrow and adipose tissue are obtained by aspiration and lipoaspiration.^[8][11]

Dental pulp and synovium extend the range of MSC sources

Gronthos and colleagues isolated a clonogenic, rapidly proliferating population from adult human dental pulp in 2000. These dental pulp stem cells shared an immunophenotype with marrow stromal cells, formed sporadic densely calcified nodules in culture and generated a dentin-pulp-like complex after transplantation in mice.^[26]

Mizuno and colleagues mapped synovium into surface (CD55+CD271−), stromal (CD55−CD271−) and perivascular (CD55−CD271+) regions. Synovial MSCs from the perivascular region showed the greatest proliferation and chondrogenic potential of the three.^[27]

Comparing yield, growth, markers and secretome across MSC source tissues

Kern and colleagues isolated MSCs from every bone marrow and adipose sample and from 63% of umbilical cord blood samples. Cord blood MSCs could be cultured longest with the highest proliferation capacity, and bone marrow MSCs had the shortest culture period.^[1]

Proliferation and population doublings

Amable and colleagues found proliferation highest in Wharton’s jelly MSCs, followed by adipose MSCs, with bone marrow MSCs slowest.^[28] Bourin and colleagues recommend the CFU-F assay for calculating the population doubling capacity of adipose-derived cells.^[5]

Over ten passages, Kozlowska and colleagues found that bone marrow and adipose MSCs kept their differentiation capacity, while marker expression declined with passage in all sources.^[29] Heo and colleagues, comparing bone marrow, adipose, placental and cord blood MSCs, found no significant differences in growth rate, colony-forming efficiency or immunophenotype.^[30]

Surface markers beyond the ISCT panel

Amable and colleagues found surface marker differences between bone marrow, adipose and Wharton’s jelly MSCs only for CD54 and CD146.^[28] Kozlowska and colleagues saw CD146 maintained in bone marrow MSCs during long-term culture and reduced in adipose MSCs.^[29]

Subramanian and colleagues reported more CD24-positive and CD108-positive cells in Wharton’s jelly than in other cord compartments, markers they used to discriminate MSCs from other mesenchymal cells.^[17]

Differentiation tendencies

Source affects lineage preference. Kern and colleagues saw no adipogenic differentiation in cord blood MSCs, and Karahuseyinoglu and colleagues found cord stromal adipocytes immature compared with marrow MSCs.^[1][14] Heo and colleagues linked DLX5 expression to osteogenic potential across sources.^[30]

Secretome differences

Amable and colleagues measured secreted proteins by Luminex and ELISA. Wharton’s jelly MSCs secreted more chemokines, inflammatory proteins and growth factors, and adipose MSCs showed a stronger pro-angiogenic profile with more extracellular matrix components and metalloproteinases.^[28]

Hsieh and colleagues found that Wharton’s jelly MSCs expressed more genes for secreted factors linked to angiogenesis and neurogenesis than bone marrow MSCs.^[31] In T cell proliferation co-culture, Heo and colleagues found the strongest inhibition with bone marrow MSCs, associated with high IL10 and TGFB1.^[30]

Within the placenta, chorionic plate MSCs inhibited phytohemagglutinin-stimulated mononuclear cell proliferation in the study by Tai and colleagues.^[24] Mattar and Bieback reviewed how bone marrow, adipose and birth-associated MSCs compare in their effects on T cell subsets, monocytes, macrophages and dendritic cells.^[3]

Donor age effects

Choudhery and colleagues compared adipose MSCs from donors under 30, 35 to 50 and over 60 years. Cells from older donors showed senescent features, fewer population doublings and lower differentiation potential.^[32]

In bone marrow, MSC number per milliliter of aspirate declined with age, and Ganguly and colleagues concluded that chronological age alone is an unreliable predictor of MSC number or potency.^[10] Perinatal tissues come from a single developmental age, which Hass and colleagues discuss as one feature of neonatal MSC sources.^[2]

Where to go from here

The ISCT minimal criteria reference explains the surface marker panel that every source on this page is measured against, and the stem versus stromal cells reference traces the naming. The MSC secretome reference describes conditioned medium and vesicle fractions, and the immunobiology reference covers HLA, IDO and PGE2.

The perinatal tissue donor eligibility reference explains how cord and placenta donors qualify, and the surface receptor chemistry and exosome references continue from cells to vesicles. Verified practices can request lot documentation, and our team is glad to discuss the methods described on this page.