In short
MSCs are commonly isolated from bone marrow, adipose tissue and umbilical cord tissue (Wharton's jelly). Cord tissue is collected after a healthy birth from tissue that is otherwise discarded, with no procedure on the donor. Published comparisons report that cord-derived MSCs expand faster and further in culture than adult bone marrow MSCs. Source is one input; lot testing still defines the product.
Anatomy of the umbilical cord
The umbilical cord connects the placenta to the baby during pregnancy. In cross-section it has a simple structure:
| Structure | What it is |
|---|---|
| Two umbilical arteries | Small, thick-walled vessels |
| One umbilical vein | A single larger vessel |
| Wharton's jelly | The gel-like connective tissue that surrounds and cushions the vessels. It is rich in hyaluronic acid and collagen and contains the stromal cells isolated as cord tissue MSCs. |
| Amniotic epithelium | The thin outer layer covering the cord |
Troyer and Weiss describe MSC-like cells in several zones of the cord: beneath the outer lining (subamnion), between the vessels (intervascular) and around the vessels (perivascular). Wharton's jelly makes up most of the cord's volume, which is one reason it is a practical source.
What counts as an MSC
The International Society for Cellular Therapy (ISCT) set minimal criteria that are still the common reference. To be called an MSC, cells must:
- Adhere to plastic under standard culture conditions
- Express CD105, CD73 and CD90 (≥95% of cells)
- Lack hematopoietic markers CD45, CD34, CD14 or CD11b, CD79α or CD19, and HLA-DR (≤2% of cells)
- Differentiate into bone, cartilage and fat cells in vitro
Troyer and Weiss reported that cells isolated from Wharton's jelly meet these criteria. Salehinejad and colleagues found CD73, CD90 and CD105 expressed, and CD34 and CD45 absent, on Wharton's jelly cells isolated by four different methods.
Cord tissue, cord blood and placenta are different sources
| Birth tissue | What is collected | Main cell types |
|---|---|---|
| Cord blood | Blood remaining in the cord and placenta after birth | Mainly hematopoietic (blood-forming) cells; MSCs are isolated from cord blood only at low frequency |
| Umbilical cord tissue | The cord itself, especially Wharton's jelly | Stromal cells that meet ISCT MSC criteria |
| Placenta and amniotic membrane | Placental tissue and the membranes around the fetus | Several cell populations, including amniotic epithelial and stromal cells |
"Cord blood stem cells" and "cord tissue MSCs" are often confused. They are different tissues with different cell populations (Hass 2011).
Comparing MSC tissue sources
| Source | Donor | How tissue is obtained | What published comparisons report |
|---|---|---|---|
| Bone marrow | Adult | Aspiration procedure on the donor | The historical reference source; age-related changes in MSC number and expansion reported (Stolzing 2008) |
| Adipose tissue | Adult | Liposuction or surgical collection from the donor | Abundant tissue source; characteristics vary with donor and collection method (Hass 2011) |
| Umbilical cord tissue (Wharton's jelly) | Neonatal | Collected after birth from tissue otherwise discarded; no procedure on the donor | Higher proliferative capacity than bone marrow MSCs (Baksh 2007); expand faster and further than adult MSCs (Troyer & Weiss 2008) |
Summary of the cited literature on sourcing and expansion. Not a comparison of effects in patients.
Why donor age matters in manufacturing
Cells from an adult donor have already aged with that donor before they reach the lab; culture expansion then adds in-vitro age on top. Stolzing and colleagues reported age-related changes in bone marrow MSC number and growth. Neonatal cord tissue starts that clock at zero, which is part of why it is used where many cells are needed from one donation. See Population Doublings & Passages for how in-vitro age is measured.
Donation and donor eligibility
Under 21 CFR Part 1271, Subpart C, every donor of human cells or tissue must be found eligible before the tissue is used. For birth tissue, eligibility is determined from the birth mother.
- Informed consent. The mother voluntarily agrees to donate tissue that would otherwise be discarded after delivery.
- Screening. Review of relevant medical records and a medical and social history interview for risk factors.
- Testing. A blood specimen from the mother is tested for relevant communicable-disease agents with donor screening tests that meet FDA requirements.
- Eligibility determination. A responsible person reviews screening and test results and documents the donor as eligible before the tissue is released for use.
- Tracking. Records link every lot back to its donation so it can be traced in either direction.
How MSCs are isolated from cord tissue
Once the cord reaches the lab, the vessels are removed and the Wharton's jelly is cut into small pieces. Cells are then released in one of two ways:
| Method | How it works | What Salehinejad 2012 reported |
|---|---|---|
| Explant culture | Tissue pieces are placed in a culture vessel and cells migrate out onto the surface | Higher cell proliferation rate |
| Enzymatic digestion | Enzymes such as collagenase break down the tissue matrix to free the cells | Collagenase/trypsin gave the highest cell yield |
The isolation method changes cell number and growth in culture, which is one reason it belongs in a supplier's process description.
From donation to vial
- Consent and donationAfter a healthy, full-term birth, the donor voluntarily consents to donate umbilical cord tissue.
- Donor eligibilityMedical and social history screening and communicable-disease testing as required under 21 CFR Part 1271, Subpart C.
- Tissue recoveryCord tissue is recovered and transported under controlled conditions.
- Isolation and expansionCells are isolated from Wharton's jelly and expanded, with passages and doublings recorded.
- Characterization and releaseCell count, viability, identity markers, sterility, endotoxin and mycoplasma testing for the lot.
- Cryopreservation and cold chainCells are frozen in a cryoprotectant at a controlled rate, stored in liquid-nitrogen vapor and shipped with documented temperature control. Viability is measured after thaw.
What the source does not tell you
Tissue source is a starting point, not a specification. Two cord tissue products can differ in donor screening, isolation method, expansion history, viability, cell count and testing. Read the source alongside the lot documentation, and be cautious of any claim that one source is universally superior.
How Stem Nova applies it
Stem Nova's 25M hUCT-MSC vial contains 25 million umbilical cord tissue-derived MSCs with 97% post-thaw viability, manufactured in the USA in an FDA-registered facility that is cGTP-compliant (21 CFR Part 1271). hUCT-MSC products are individualized and not FDA-approved. Use is clinician-directed, and patients should consult their primary care provider.
What to ask your supplier
- Which tissue are the cells isolated from: cord tissue, cord blood or placenta?
- How was the donor screened and tested, and who made the eligibility determination?
- Were cells isolated by explant or enzymatic digestion?
- Do the cells meet ISCT identity criteria, and is that tested on my lot?
- What are the passage number and cumulative population doublings at harvest?
- What are the cell count and post-thaw viability, and who measured them?
- Is the facility FDA-registered and cGTP-compliant (21 CFR Part 1271)?
Frequently asked questions
What is Wharton's jelly?
The gel-like connective tissue of the umbilical cord that surrounds the two arteries and one vein. It contains the stromal cells isolated as umbilical cord tissue MSCs.
Are umbilical cord tissue MSCs the same as cord blood stem cells?
No. Cord blood is collected from the blood in the cord and placenta and is mainly a source of hematopoietic (blood-forming) cells. Cord tissue MSCs come from the cord's connective tissue, Wharton's jelly.
Does collecting cord tissue involve the baby or mother?
Cord tissue is collected after birth from tissue that would otherwise be discarded, with the donor's voluntary consent. There is no procedure on the donor.
Who is tested when cord tissue is donated?
The birth mother. Her medical and social history is reviewed and a blood specimen is tested for relevant communicable-disease agents under 21 CFR Part 1271, Subpart C.
What is the regulatory status of hUCT-MSC products?
Stem Nova's hUCT-MSC products are not FDA-approved. They are individualized biologics; use is clinician-directed, and patients should consult their primary care provider.
Is one MSC source the best?
Published studies report differences in how cells from each source expand in culture. Source alone does not define a product; expansion history and lot testing matter as much.
References
- Dominici M, Le Blanc K, Mueller I, et al. Cytotherapy. 2006;8(4):315-317. doi:10.1080/14653240600855905. Cited for: ISCT minimal criteria for defining MSCs.
- Troyer DL, Weiss ML. Stem Cells. 2008;26(3):591-599. doi:10.1634/stemcells.2007-0439. Cited for: Wharton's jelly cells and MSC criteria.
- Baksh D, Yao R, Tuan RS. Stem Cells. 2007;25(6):1384-1392. doi:10.1634/stemcells.2006-0709. Cited for: proliferative capacity, umbilical cord vs. bone marrow.
- Hass R, Kasper C, Böhm S, Jacobs R. Cell Commun Signal. 2011;9:12. doi:10.1186/1478-811X-9-12. Cited for: comparison of adult and neonatal MSC sources.
- Stolzing A, Jones E, McGonagle D, Scutt A. Mech Ageing Dev. 2008;129(3):163-173. doi:10.1016/j.mad.2007.12.002. Cited for: donor-age changes in bone marrow MSCs.
- Salehinejad P, Alitheen NB, Ali AM, et al. In Vitro Cell Dev Biol Anim. 2012;48(2):75-83. doi:10.1007/s11626-011-9480-x. Cited for: Wharton's jelly isolation methods compared.
- U.S. Code of Federal Regulations, Title 21, Part 1271: Human Cells, Tissues, and Cellular and Tissue-Based Products. eCFR. Cited for: cGTP and donor eligibility requirements.
Citations support manufacturing, characterization and sourcing facts only. They are not claims about any Stem Nova product's effect in the body.