What Can Placenta Stem Cells Be Used For?

Placenta-derived stem cells are being investigated for a surprisingly wide range of medical uses, from treating blood cancers and healing chronic wounds to repairing damaged hearts and calming overactive immune systems. The most established application involves hematopoietic stem cells from umbilical cord blood, which have been used for decades to treat leukemia and other blood disorders. Beyond that well-proven use, mesenchymal stem cells harvested from different layers of the placenta are now the focus of early-stage clinical trials in areas as varied as multiple sclerosis, liver fibrosis, type 1 diabetes, and graft-versus-host disease.

Why the Placenta Is a Useful Source of Stem Cells

The placenta is rich in multiple types of stem cells, and each region of the organ yields cells with slightly different properties. Researchers have isolated mesenchymal stem cells (MSCs) from at least four distinct placental zones: the amniotic membrane, the chorionic membrane, the chorionic plate, and the chorionic villi. Cells from all four regions share the standard surface markers that define MSCs and can differentiate into bone-forming cells, but they differ in their ability to form cartilage and fat tissue.¹ Placenta-derived stem cells sit somewhere between embryonic and adult stem cells in terms of versatility: they can give rise to cell types from all three embryonic germ layers, yet they do not carry the tumor-forming risk associated with embryonic stem cells.²

This combination of flexibility and safety is one reason the placenta has attracted so much research attention. Compared to bone marrow, which requires an invasive extraction procedure, the placenta is normally discarded after birth. Collecting it raises no ethical controversy and poses no physical risk to the mother or child. Its large size also means a single placenta can yield a substantial number of cells for banking and future therapeutic use.

The Established Use: Cord Blood Transplants for Blood Cancers

The most clinically proven application of placenta-associated stem cells is the transplantation of hematopoietic stem cells from umbilical cord blood. Cord blood has become an important alternative source of blood-forming stem cells for patients with leukemia and other blood cancers who lack a fully matched bone marrow donor.³ This matters because many patients, especially those from underrepresented ethnic groups, cannot find a perfectly matched unrelated donor in bone marrow registries.

In acute myeloid leukemia specifically, cord blood transplantation cures roughly 30 to 40 percent of adults and 60 to 70 percent of children.⁴ The development of double-unit cord blood transplantation, where cells from two separate donors are combined, has extended the approach to larger children and adults who need a bigger cell dose than a single cord blood unit can provide.⁵ This is the one area where placenta-related stem cells are used routinely in hospitals today, not just in experimental trials.

Calming the Immune System

One of the most promising properties of placental MSCs is their ability to dial down inflammation and rein in an immune system that has gone haywire. In laboratory studies, human placental MSCs have been shown to dampen the NF-κB signaling pathway, a central switch in the body’s inflammatory response, by reducing the activity of a receptor called TLR4 and lowering the phosphorylation of key downstream proteins.⁶ In practical terms, these cells can quiet inflammation without broadly suppressing the immune system the way a drug like prednisone does.

That immunomodulatory talent has been put to use in one of the most dangerous complications of bone marrow transplantation: graft-versus-host disease (GvHD), where donor immune cells attack the recipient’s organs. In a phase I/II trial, placenta-derived decidua stromal cells were given to 21 patients with severe gastrointestinal GvHD. Every patient responded, and one-year survival reached 81 percent.⁷ An earlier study found that among steroid-refractory GvHD patients, one-year survival with decidua stromal cells was 73 percent in one treatment group, compared to just 3 percent in historical controls who received standard care.⁸ Those numbers are striking, though the studies are small and unblinded, so they need to be confirmed in larger trials.

Heart Repair After a Heart Attack

Several animal studies suggest placental stem cells can help a damaged heart recover after a heart attack. In mouse models, cells isolated from the placenta that express a protein called CDX2 were able to home specifically to injured heart tissue, where they differentiated into heart muscle cells and blood vessel cells and improved how well the heart pumped.⁹ A separate line of research using a commercial placental stromal cell product called PLX-PAD showed that treated mice developed smaller areas of dead heart tissue, thicker heart walls, and more new blood vessels in the zone around the injury compared to untreated controls.¹⁰

Among different placental cell types, first-trimester placental MSCs appear to outperform both later-pregnancy placental cells and bone marrow MSCs in rat models of heart attack, likely because they produce higher levels of pro-blood-vessel-growth genes.¹¹ None of this work has advanced to large human trials yet. The mechanism seems to center on encouraging new blood vessel growth and reducing cell death in the damaged area, rather than wholesale replacement of lost heart muscle.

Multiple Sclerosis and Neurological Disease

Placental MSCs have been tested in small human trials for multiple sclerosis, a disease where the immune system attacks the protective sheath around nerve fibers. In a phase 1 trial of five patients with secondary-progressive MS, treatment with placenta-derived MSCs led to improvements in disability scores, brain connectivity on imaging, and markers of inflammation over six months. Anti-inflammatory cytokine levels rose, while pro-inflammatory markers fell significantly.¹² An earlier randomized trial also evaluated a placenta-derived cell preparation called PDA-001 in adults with MS, marking one of the first controlled studies exploring this approach for neurological disease.¹³

The phase 1 trial was designed to assess safety and feasibility, not to prove the treatment works. Five patients is far too few to draw firm conclusions about effectiveness. But the signals were encouraging enough that the researchers called for larger phase II trials. For a disease like secondary-progressive MS, where existing treatments have limited success, even tentative evidence of improvement attracts serious interest.

Healing Chronic Wounds

Diabetic foot ulcers are among the most frustrating problems in medicine: they heal slowly, recur often, and sometimes lead to amputation. Placental tissues share a structural resemblance to skin, with the amniotic membrane containing layers that mirror the epidermis, dermis, and subcutaneous tissue. That similarity, combined with the growth factors and MSCs present in placental tissue, makes it a natural candidate for wound-healing applications.¹⁴

In a randomized clinical trial, patients with diabetic foot ulcers who received human placental MSCs on a nanofibrous scaffold saw wound size shrink by roughly 66 to 71 percent, compared to just 36 percent in the control group. The treated groups also experienced better pain-free walking distance, and biopsies showed new capillary formation in the implanted tissue.¹⁵ Beyond diabetic wounds, a meta-analysis of preclinical studies on MSC-derived exosomes (tiny packets of biological material shed by the cells) found large benefits in wound healing rate, new blood vessel density, re-epithelialization, collagen deposition, and scar width reduction compared to controls.¹⁶

Liver Fibrosis and Liver Regeneration

When the liver is repeatedly injured, whether by alcohol, hepatitis, or toxins, it scars. That scarring, called fibrosis, can eventually progress to cirrhosis and liver failure. In animal models, placental MSCs have shown a clear anti-fibrotic effect. Chorionic-plate-derived MSCs reduced markers of scarring and collagen buildup in rats with chemically induced liver fibrosis, while boosting levels of enzymes that break down scar tissue.¹⁷ A follow-up study showed that human placental MSCs reduced fibrosis in mice by restoring levels of a protein called Caveolin-1 in the liver’s stellate cells, which shut down a key scarring pathway. The treatment worked better against mild-to-moderate fibrosis than against severe fibrosis.¹⁸

A related line of research has explored whether you even need to transplant the cells themselves. Extracellular vesicles, essentially cargo packets released by placental MSCs, were given to mice before partial removal of the liver and promoted liver regeneration. The vesicles delivered specific molecules that enhanced liver cell proliferation both in the lab dish and in the living animal.¹⁹ If cell-free approaches like this prove effective in humans, they could sidestep many of the logistical challenges of cell transplantation, including the need for living cells, cold storage, and precise dosing.

Type 1 Diabetes and Insulin Production

Type 1 diabetes is caused by the immune system destroying the insulin-producing beta cells of the pancreas. Placental MSCs have shown an ability to differentiate into insulin-producing cells in the lab and, when transplanted into diabetic mice, to restore normal blood sugar levels.²⁰ The same team also generated islet-like cell clusters from placental MSCs that achieved the same result, suggesting more than one route from placental cells to functional insulin production.

A phase 1 clinical trial in humans with type 1 diabetes tested placental MSC transplantation for safety. Over one year of follow-up, no serious adverse events occurred, and two patients experienced partial remission and fewer episodes of dangerously low blood sugar in the month after treatment. Antibodies associated with the autoimmune attack on beta cells dropped for the first three months before rising again.²¹ The temporary nature of the antibody drop hints that repeated infusions or combination therapies may be needed to sustain the benefit, a challenge that runs through most autoimmune applications of cell therapy.

Joint and Cartilage Repair

Cartilage has almost no ability to repair itself once damaged, which is why osteoarthritis tends to be a one-way street. In a pilot human study, patients with knee osteoarthritis who received placental MSC injections showed about a 10 percent improvement in cartilage thickness across the total knee joint area over 24 weeks, though there was no significant healing in the meniscus or ligaments.²² In a rabbit model, transplanting placental MSCs combined with a hyaluronic acid hydrogel scaffold produced better-quality cartilage repair tissue than either no treatment or the scaffold alone.²³

A 10 percent gain in cartilage thickness is modest, and a pilot study with no control group has obvious limitations. But considering that no existing drug can regrow cartilage at all, even incremental gains attract attention from orthopedic researchers. The approach may eventually be paired with physical rehabilitation or growth factors to amplify the effect.

Critical Limb Ischemia and Blood Vessel Growth

Critical limb ischemia, a condition where blood flow to the legs is so restricted that tissue begins to die, is another area where placental cells show potential. Research has highlighted that different regions of the placenta produce different growth factors relevant to blood vessel formation. Chorionic-plate-derived MSCs secrete high levels of HGF and VCAM-1, which promote new blood vessel growth, while decidual-plate MSCs secrete more VEGF and angiopoietin-1, making them candidates for treating limb ischemia.²⁴

A phase 1 clinical trial tested placental MSCs in patients with critical limb ischemia at doses up to 60 million cells. All doses were well tolerated, and blood tests showed no sign that the patients’ immune systems mounted an attack against the transplanted cells.²⁵ Safety data like this is a prerequisite for larger efficacy trials. The fact that allogeneic (donor-derived) placental cells did not trigger immune rejection is a meaningful finding, because it means patients would not necessarily need cells from their own placenta.

Eye Diseases and Corneal Engineering

The amniotic membrane, the innermost layer of the placental sac, has been used in eye surgery for years as a biological bandage for damaged corneas. Its anti-inflammatory and anti-scarring properties help heal the eye’s surface after injury, surgery, or disease. Umbilical cord serum, another placenta-associated product, contains growth factors and neurotrophic factors that support corneal nerve regeneration and surface repair in conditions like severe dry eye and ocular graft-versus-host disease.

More recently, researchers have used placental MSCs for something far more ambitious: 3D bioprinting of corneal tissue. A study demonstrated that human placental MSCs encapsulated in a bioink made from decellularized corneal tissue could be printed into cornea-shaped constructs without needing an external scaffold or mold. The cells maintained high viability and began to elongate into a morphology resembling natural corneal cells by two weeks.²⁶ This is still at the laboratory stage, but it points toward a future where donor corneas, which are in perennial short supply worldwide, could be manufactured rather than harvested.

Not All Placental MSCs Are the Same

A detail that often gets lost in media coverage is that “placental stem cells” is not a single entity. Cells from the amniotic membrane, chorionic plate, decidual plate, and umbilical cord all qualify, and they behave differently. Amniotic membrane MSCs secrete more of the chemical signals associated with ovarian aging treatments. Chorionic plate MSCs show stronger blood-vessel-forming potential. Decidual plate MSCs lean toward limb ischemia applications. And umbilical cord MSCs produce the broadest range of helpful signaling molecules overall.²⁴ One of the major phenotypic differences is the expression of the surface marker CD106, which is very high on chorionic plate MSCs, moderate on umbilical cord MSCs, and nearly absent on decidual plate MSCs.²⁴

This variability means that the best cell type for a given disease may depend on which part of the placenta the cells came from. Future clinical applications will likely involve selecting a specific placental cell population tailored to the condition being treated, rather than using a generic “placental stem cell” product.

Placental Banking and the Regulatory Landscape

Cord blood banking, either through public registries or private family banks, is well established in many countries. There is growing interest in extending that infrastructure to include non-hematopoietic cells from placental tissue. Banking these cells alongside cord blood could lay the groundwork for future regenerative medicine trials and therapies without requiring a separate collection procedure.

Regulatory oversight matters here, because the stem cell space is plagued by clinics offering unproven treatments for large fees. Federal courts have unanimously affirmed the FDA’s authority to regulate stem cell interventions, and financial penalties against providers of unapproved treatments have increased significantly.²⁷ Any clinic offering placental stem cell therapy outside of a registered clinical trial should be viewed with serious skepticism. Legitimate therapies go through phased trials that establish safety and then effectiveness before they reach patients. The applications described in this article range from well-established (cord blood transplants) to early experimental (bioprinted corneas), and the gap between those extremes is measured in years of rigorous testing, not marketing brochures.

Cell-Free Approaches and the Exosome Frontier

One of the more intriguing directions in the field is the idea that you might not need the cells at all. MSCs appear to do much of their therapeutic work not by engrafting permanently into injured tissue, but by releasing signaling molecules and extracellular vesicles that instruct local cells to heal. If the therapeutic cargo can be isolated, standardized, and stored more easily than living cells, it could dramatically simplify manufacturing and delivery. The liver regeneration study using placental MSC vesicles is one example of this approach in action.¹⁹ The wound-healing meta-analysis of exosome therapies adds preclinical weight to the concept, showing large effect sizes across multiple outcome measures in animal models.¹⁶

Cell-free therapies could also ease regulatory hurdles. A vial of exosomes is closer to a pharmaceutical product than a living cell preparation, and pharmaceutical products have a well-worn pathway through regulatory approval. Whether the clinical results hold up when you strip the cells out and keep only what they secrete remains an open question, but it is being pursued aggressively in wound healing, liver disease, and cosmetic dermatology.