The placenta and the membranes that surround a baby in the womb are usually discarded after birth, yet they hold several kinds of cells that researchers can isolate and grow in the laboratory. Scientists call these birth tissues perinatal tissues. The main sources are the placenta itself, the chorion, the amniotic membrane and the amniotic fluid; the umbilical cord, including its Wharton’s jelly, belongs to the same family.[1] This guide explains where each tissue sits, which cells come from it, how the cells are obtained and what has been tested in people so far, as part of the wider field of regenerative medicine.
What Are Perinatal (Birth-Tissue) Stem Cells?
Perinatal cells are cells taken from tissues that form during pregnancy and are delivered with the baby. Most of the research focuses on two groups: mesenchymal stromal cells, which are spindle-shaped support cells found in the connective tissue of the placenta and membranes, and epithelial cells from the amniotic membrane.[2] The placenta is available at every birth, collecting it does not involve an invasive procedure for mother or baby, and its use does not raise the ethical objections attached to embryonic stem cells.
Perinatal cells sit between embryonic and adult cells. They are often grouped with somatic (adult-type) stem cells because they are collected at birth from tissue that is not part of the baby’s body, but some of them keep features of very early development. The tissues themselves form very early: the outer layer of the blastocyst that gives rise to the placenta is set apart before the embryo proper exists, and amniotic epithelial cells develop from the epiblast about eight days after fertilization, before the embryo forms its three germ layers. Amniotic epithelial cells also carry some markers normally seen on embryonic stem cells.[3]
Placenta-derived stem cells are mostly mesenchymal stromal cells, which differ from the blood-forming (hematopoietic) stem cells found in umbilical cord blood (UCB) and bone marrow. Blood disorders such as leukemia, sickle cell anemia and thalassemia can be treated, in selected patients, with hematopoietic stem cell transplants, and placental cells are not an established treatment for them.
The Four Birth-Tissue Sources Compared
The term “placenta stem cells” is used loosely, and it often hides the fact that different parts of the placenta give different cells. The placenta has a fetal side, made up of the chorion and the amniotic membrane fused to it, and a maternal side, the basal decidua, which comes from the lining of the mother’s uterus. Cells from the basal plate can therefore be of fetal or maternal origin, and researchers are expected to state which tissue a cell came from and to check whether it is fetal or maternal.[1]
| Source | Where it is | Main cells studied | How it is obtained |
|---|---|---|---|
| Placenta (chorionic villi and basal plate) | The disc attached to the wall of the uterus; the basal plate contains the mother’s decidua | Mesenchymal stromal cells from the villi; decidual stromal cells, which are maternal | After delivery |
| Chorion | The outer fetal membrane: the chorionic plate covers the fetal face of the placenta and the smooth chorion lines the rest of the sac | Chorionic mesenchymal stromal cells; trophoblast cells | After delivery, separated from the amnion |
| Amniotic membrane | The thin innermost membrane that lines the amniotic sac and faces the fluid | Amniotic epithelial cells and amniotic mesenchymal stromal cells | After delivery, peeled away from the chorion |
| Amniotic fluid | The fluid inside the sac, which contains cells shed by the fetus and the membranes | A mixed population that includes mesenchymal-like cells and a small subset of c-kit (CD117) positive stem cells | From a sample taken at amniocentesis, or at caesarean birth |
| Umbilical cord, for comparison | Cord tissue (Wharton’s jelly) and the blood inside the cord | Mesenchymal stromal cells in the tissue; blood-forming stem cells in cord blood | After birth |
The amniotic membrane has two cell layers. A sheet of epithelial cells rests directly on the fluid, and a layer of mesenchymal stromal cells lies in the connective tissue beneath it. Where the amnion covers the placenta, it is fused to the chorionic plate; over the rest of the sac, it lies against the smooth chorion.[1]
Amniotic Fluid and Amniotic Membrane Cells
Amniotic fluid cells and amniotic membrane cells are often discussed together, but they are collected in very different ways. Amniotic fluid cells come from fluid drawn during pregnancy, usually from amniocentesis performed for prenatal testing, or from fluid collected at caesarean birth.[1] Amniotic membrane cells come from the membrane, which is collected after birth with the rest of the placenta.
In one study, fluid taken at amniocentesis between 16 and 18 weeks of pregnancy yielded spindle-shaped cells that carried the standard mesenchymal markers (CD73, CD90 and CD105), lacked blood-cell markers, and could be turned into bone-forming and fat-forming cells in culture; cells from younger mothers grew faster.[4] A smaller subset of amniotic fluid cells selected for the c-kit marker has been grown into cell lines that kept a normal karyotype over long culture and, in laboratory tests, developed into fat, bone, muscle, blood-vessel, nerve-like and liver-like cells; these lines did not form tumors when tested in animals.[5]
Amniocentesis itself carries a small risk of complications, including miscarriage. A 2019 analysis of more than 63,000 procedures estimated the extra risk of miscarriage caused by the procedure at about 0.3 percent, roughly 1 in 300, and lower still when women were compared with others of similar background risk.[6] Amniocentesis is performed to diagnose conditions in the baby. It is not done just to collect cells, and amniotic membrane collected after birth involves no procedure on the mother or baby.
Results like these show what the cells can do in a culture dish or in an animal. They do not show that the same cells repair human tissue after they are given to a patient. That question can only be answered in controlled clinical trials.
Low HLA Class II Expression: What It Does and Does Not Mean
HLA (human leukocyte antigen) molecules on the surface of cells let the immune system tell “self” from “non-self”. Mesenchymal stromal cells, including those from the placenta, are defined in part by the absence of the class II molecule HLA-DR under standard culture conditions.[7] Low class II expression makes the cells less likely to provoke a strong response from helper T cells, which is why mesenchymal stromal cells were long described as “immune privileged” and why donor cells are given in trials without tissue matching. It does not make them invisible to the immune system. Donor mesenchymal stromal cells still carry class I HLA molecules, patients can make antibodies against them, and they can be rejected; a 2014 review found that how much this affects any benefit had not been established.[8]
Umbilical Cord Vs. Placenta Derived
Umbilical cord blood, umbilical cord tissue and the placenta are all collected after birth from tissue that would otherwise be discarded, and cells from each can be frozen and stored through cell banking. They are used for different things. Cord blood contains blood-forming stem cells. It is an established alternative to bone marrow and blood as a source of these cells for transplants that rebuild the blood and immune system, and cord blood from related and unrelated donors has been used for a range of blood disorders and inherited metabolic diseases.[9] Cord tissue and the placenta yield mostly mesenchymal stromal cells, which do not rebuild blood and are studied instead for their effects on inflammation and tissue repair.
Placenta-derived cells are therefore not a transplant source for blood disorders. Any stem cell transplant for a blood disorder is an intensive procedure with serious risks, and whether it is the right treatment depends on the specific disease and the patient.
How Birth Tissues Are Collected and Processed
Placental tissue is collected after a vaginal or caesarean birth, with the mother’s informed consent. Because the tissue belongs to the newborn, it is the mother who is tested for infections. In the United States, for example, federal rules require donor testing for relevant infectious diseases and, for a donor one month of age or younger, testing of a specimen from the birth mother.[10] In the laboratory, the membranes are separated from the placenta, the amnion is peeled from the chorion, and each tissue is cut into small pieces and treated with enzymes that free the cells. The cells are then grown in culture, counted and characterized, and can be frozen for later use. Isolation methods differ from one laboratory to the next, which is one reason results from different groups are hard to compare.[2]
What Has Been Tested in People
Results from clinical studies of birth tissues are published in peer-reviewed medical journals. Two kinds of use need to be kept apart: grafts of the tissue itself, and cell therapies made from cells grown out of the tissue.
Tissue grafts. Amniotic membrane has been used as a surgical graft on the eye since the 1940s, when it was first used for ocular burns. It is a useful option for some eye conditions, although a 2004 review judged that it was being used well beyond its proven benefit.[11] Dried amnion and chorion membranes are also used as dressings for diabetic foot ulcers; a 2022 analysis of 11 randomized trials found more ulcers fully healed when the membrane was added to standard wound care.[12] These are tissue products placed on a wound, not living stem cells given as a treatment.
Cell therapies. The table lists published examples of trials that gave placenta- or amnion-derived cells to patients. It is not a complete list.
| Cells | Condition | Study | What it found |
|---|---|---|---|
| Placenta-derived stromal cells (PLX-PAD), injected into the leg muscle | Critical limb ischaemia in patients who could not have revascularization | Phase III, randomized, placebo-controlled, 213 patients | No benefit: amputation or death occurred at similar rates with cells and placebo. A post hoc subgroup without poorly controlled diabetes did better, which needs confirmation.[13] |
| PLX-PAD, injected into the hip muscle during surgery | Muscle injury from hip replacement | Phase I/IIa, randomized, placebo-controlled, 20 patients | Better muscle strength and volume with the lower dose.[14] A phase III trial in hip fracture patients was designed afterwards; its results had not been published at the time of writing.[15] |
| Placenta-derived cells (PDA-001), into a vein | Moderate to severe Crohn’s disease | Phase 1b/2a, partly randomized, 50 patients | Clinical response in 36 percent with cells and none with placebo, but serious adverse events in 32 percent with cells against 7 percent with placebo.[16] |
| Placenta-derived cells (PDA-002), into the leg muscle | Diabetic foot ulcers | Phase 2, randomized, placebo-controlled, 159 patients, sponsored by the manufacturer | The best healing rate was seen with the lowest dose in patients with peripheral artery disease (38.5 percent against 22.6 percent with placebo).[17] |
| Placenta-derived decidual stromal cells, into a vein | Severe acute graft-versus-host disease after a bone marrow transplant | Phase I/II, no control group, 21 patients | All patients responded, 11 completely; the authors state that randomized trials are needed.[18] |
| Placenta-derived mesenchymal stromal cells, into a vein | Idiopathic pulmonary fibrosis | Phase 1b, no control group, 8 patients | Well tolerated; lung function and CT scans unchanged after six months.[19] |
| PDA-001, into a vein | Multiple sclerosis | Phase 1b, randomized, placebo-controlled, 16 patients | Safe, with no worsening of brain lesion counts on MRI.[20] |
| Amniotic epithelial cells, into a vein | Bronchopulmonary dysplasia in premature babies | Phase I, no control group, 6 infants | The first baby had a short episode of heart and breathing compromise during the infusion; after the method was changed, no further events occurred.[21] |
| Amniotic epithelial cells, into a vein | Compensated liver cirrhosis | Phase I, no control group, 9 patients | No serious adverse events in the first 56 days; a short-lived fall in platelet count in all patients.[22] |
| Amniotic epithelial cells, injected into the fistula | Perianal fistulas in Crohn’s disease | Phase I, no control group, 10 patients | Safe and well tolerated; complete response in 4 and partial response in 4.[23] |
The largest controlled trial so far, the phase III limb ischaemia trial, found no benefit on its main outcome. The positive results in the other studies come from small trials, trials without a control group, or subgroups, and they still need to be confirmed in larger controlled trials. Until then, no condition can be called treatable with placenta- or amnion-derived cells.
Published Clinical Citations
[1] ^ Silini AR, Di Pietro R, Lang-Olip I, Alviano F, et al. Perinatal derivatives: where do we stand? A roadmap of the human placenta and consensus for tissue and cell nomenclature. Frontiers in Bioengineering and Biotechnology. 2020;8:610544. https://doi.org/10.3389/fbioe.2020.610544
[2] ^ Parolini O, Alviano F, Bagnara GP, et al. Concise review: isolation and characterization of cells from human term placenta: outcome of the first international Workshop on Placenta Derived Stem Cells. Stem Cells. 2008;26(2):300-311. https://doi.org/10.1634/stemcells.2007-0594
[3] ^ Miki T, Lehmann T, Cai H, Stolz DB, Strom SC. Stem cell characteristics of amniotic epithelial cells. Stem Cells. 2005;23(10):1549-1559. https://doi.org/10.1634/stemcells.2004-0357
[4] ^ Borzou B, Mehrabani D, Zare S, Zamani-Pereshkaft M, Acker JP. The effect of age and type of media on growth kinetics of human amniotic fluid stem cells. Biopreservation and Biobanking. 2020;18(5):389-394. https://doi.org/10.1089/bio.2019.0103
[5] ^ De Coppi P, Bartsch G, Siddiqui MM, et al. Isolation of amniotic stem cell lines with potential for therapy. Nature Biotechnology. 2007;25(1):100-106. https://doi.org/10.1038/nbt1274
[6] ^ Salomon LJ, Sotiriadis A, Wulff CB, Odibo A, Akolekar R. Risk of miscarriage following amniocentesis or chorionic villus sampling: systematic review of literature and updated meta-analysis. Ultrasound in Obstetrics & Gynecology. 2019;54(4):442-451. https://doi.org/10.1002/uog.20353
[7] ^ Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315-317. https://doi.org/10.1080/14653240600855905
[8] ^ Ankrum JA, Ong JF, Karp JM. Mesenchymal stem cells: immune evasive, not immune privileged. Nature Biotechnology. 2014;32(3):252-260. https://doi.org/10.1038/nbt.2816
[9] ^ Ballen KK, Gluckman E, Broxmeyer HE. Umbilical cord blood transplantation: the first 25 years and beyond. Blood. 2013;122(4):491-498. https://doi.org/10.1182/blood-2013-02-453175
[10] ^ US Code of Federal Regulations. Title 21, section 1271.80: What are the general requirements for donor testing? https://www.ecfr.gov/current/title-21/chapter-I/subchapter-L/part-1271/subpart-C/section-1271.80
[11] ^ Dua HS, Gomes JA, King AJ, Maharajan VS. The amniotic membrane in ophthalmology. Survey of Ophthalmology. 2004;49(1):51-77. https://doi.org/10.1016/j.survophthal.2003.10.004
[12] ^ Mohammed YA, Farouk HK, Gbreel MI, et al. Human amniotic membrane products for patients with diabetic foot ulcers. Do they help? A systematic review and meta-analysis. Journal of Foot and Ankle Research. 2022;15(1):71. https://doi.org/10.1186/s13047-022-00575-y
[13] ^ Norgren L, Weiss N, Nikol S, et al. PACE: randomized, controlled, multicentre, multinational, phase III study of PLX-PAD for critical limb ischaemia in patients unsuitable for revascularization: randomized clinical trial. British Journal of Surgery. 2024;111(2):znad437. https://doi.org/10.1093/bjs/znad437
[14] ^ Winkler T, Perka C, von Roth P, et al. Immunomodulatory placental-expanded, mesenchymal stromal cells improve muscle function following hip arthroplasty. Journal of Cachexia, Sarcopenia and Muscle. 2018;9(5):880-897. https://doi.org/10.1002/jcsm.12316
[15] ^ Winkler T, Costa ML, Ofir R, et al. HIPGEN: a randomized, multicentre phase III study using intramuscular PLacenta-eXpanded stromal cells therapy for recovery following hip fracture arthroplasty: a study design. Bone & Joint Open. 2022;3(4):340-347. https://doi.org/10.1302/2633-1462.34.BJO-2021-0156.R1
[16] ^ Melmed GY, Pandak WM, Casey K, et al. Human placenta-derived cells (PDA-001) for the treatment of moderate-to-severe Crohn’s disease: a phase 1b/2a study. Inflammatory Bowel Diseases. 2015;21(8):1809-1816. https://doi.org/10.1097/MIB.0000000000000441
[17] ^ Pollak R, Anderson J, Altmanshofer B, et al. Human placenta-derived cells (PDA-002) in diabetic foot ulcer patients with and without peripheral artery disease: a phase 2 multi-center, randomised, double-blind, placebo-controlled trial. International Wound Journal. 2025;22(10):e70769. https://doi.org/10.1111/iwj.70769
[18] ^ Ringdén O, Sadeghi B. Placenta-derived decidua stromal cells: a new frontier in the therapy of acute graft-versus-host disease. Stem Cells. 2024;42(4):291-300. https://doi.org/10.1093/stmcls/sxae003
[19] ^ Chambers DC, Enever D, Ilic N, et al. A phase 1b study of placenta-derived mesenchymal stromal cells in patients with idiopathic pulmonary fibrosis. Respirology. 2014;19(7):1013-1018. https://doi.org/10.1111/resp.12343
[20] ^ Lublin FD, Bowen JD, Huddlestone J, et al. Human placenta-derived cells (PDA-001) for the treatment of adults with multiple sclerosis: a randomized, placebo-controlled, multiple-dose study. Multiple Sclerosis and Related Disorders. 2014;3(6):696-704. https://doi.org/10.1016/j.msard.2014.08.002
[21] ^ Lim R, Malhotra A, Tan J, et al. First-in-human administration of allogeneic amnion cells in premature infants with bronchopulmonary dysplasia: a safety study. Stem Cells Translational Medicine. 2018;7(9):628-635. https://doi.org/10.1002/sctm.18-0079
[22] ^ Lim R, Hodge A, Warner S, et al. Human amniotic epithelial cell transplantation is safe and well tolerated in patients with compensated cirrhosis: a first-in-human trial. Stem Cells Translational Medicine. 2024;13(6):522-531. https://doi.org/10.1093/stcltm/szae023
[23] ^ Keung C, Nguyen TC, Lim R, Gerstenmaier A, Sievert W, Moore GT. Local fistula injection of allogeneic human amnion epithelial cells is safe and well tolerated in patients with refractory complex perianal Crohn’s disease: a phase I open label study with long-term follow up. EBioMedicine. 2023;98:104879. https://doi.org/10.1016/j.ebiom.2023.104879