Mesenchymal stromal cells from human perinatal tissues: From biology to cell therapy

Table 1 Comparison of different perinatal sources of mesenchymal stromal cells regarding mesenchymal stromal cell characteristics

Source of MSCs	Isolation	Origin	Isolation efficacy	Frequency	Expansion potential	Immunephenotype	Differentiationa	Immuno-suppression	Senescence/genetic stability/safety	Ref.
Cord blood	Ficoll gradient Lineage depletion	Fetal	At best 60%	Very rare, 1/108 MNC Inverse correlation with gestational age	Dependent on seeding density	SSEA-3, SSEA-4, TRA 1-60, TRA 1-82, Nanog	Osteogenic Chondrogenic Adipogenic-significantly reduced compared to adult MSC endothelial	Inhibition of T cell proliferation	Cells senescence Stable Karyotype Non tumorigenic	[20,32] and own unpublished data[49,61,93,95,96]
Umbilical Cord (Wharton´s jelly) Including UC matrix stem cells, UC perivascular cells, UC stroma cells	Removal of vein and arteries Mechanical dissection, Collagenase + hyaluronidase digestion	Fetal	100%	10-50 × 103 /cm UC	High Expansion potential	20% no HLA class I, nor class II SSEA-4, TRA 1-60	Osteogenic Chondrogenic Adipogenic-significantly reduced compared to adult MSC Neurogenic Myogenic, cardiac endothelial	Inhibition of T cell proliferation	Late senescence Telomerase Stable karyotype Non-tumorigenic	Reviewed in [59,95,97]
Amniotic Fluid	Centrifugation	Fetal	21/23 samples	Frequency 3 CFU-f/mL AF range 1-6 0.9%-1.5%	Expansion significantly higher than for BM-MSCs doubling time 18 h	Lower expression of CD44 and CD105 compared to BM-MSCs 90% positive for Oct-4	Osteogenic Adipogenic Chondrogenic Hepatogenic Neurogenic Myogenic, cardio	Inhibition of T cell proliferation	Longer telomeres than BM-MSCs Stable karyotype Non tumorigenic	[95,98]
Placenta (Amnion, chorion and decidua basalis)	dissection digestion with collagenase and DNase, Percoll gradient	Fetal/maternal	62.5%-100%		Expansion significantly higher than for BM-MSC	SSEA-4, TRA 1-60, TRA 1-81	Osteogenic Chondrogenic Adipogenic-significantly reduced compared to adult MSC	Inhibition of T cell proliferation	Cells senescence Rarely chromosomal changes no transformation No toxicity when injecting 1x107MSC/kg	[26,50,99,100]
Amnion (contains besides MSCs amniotic epithelial cells)	Mechanical peeling, mincing Trypsin treatment, digestion with collagenase or/and DNase	Fetal		4 × 106/100 cm2 starting material Or 1 × 106 /g of tissue	First trimester proliferate better than third trimester	SSEA-3, SSEA-4, Nanog	Adipogenic Chondrogenic Osteogenic Myogenic, skeletal Myogenic, cardio Angiogenic Neurogenic Pancreatic	Inhibition of T cell proliferation	Cells senescence Stable Karyotype Non tumorigenic	Reviewed in [21] [95,101,102]
Chorion (contains besides MSCs chorionic trophoblastic cells)	Mechanical removal, dispase and collagenase digestion	Fetal			Expansion significantly higher than for BM-MSC		Adipogenic Chondrogenic Osteogenic Myogenic, skeletal Neurogenic	Inhibition of T cell proliferation	Cells senescence Stable Karyotype Non tumorigenic	Reviewed in [21]

^aDifferentiation potential assessedin vitroand in non-clonal cultures. MSCs: Mesenchymal stromal cells; UC: Umbilical cord; AF: Amniotic fluid-derived.

Table 2 Current clinical trials listed at http://www.clinicaltrials.gov (research August 2010) employing mesenchymal stromal cells from umbilical cord blood, umbilical cord or placenta or case studies applying mesenchymal stromal cells from perinatal sources

UCB-MSCs	Safety and efficacy study of umbilical cord blood-derived mesenchymal stem cells to promote engraftment of unrelated hematopoietic stem cell transplantation
UCB-MSCs	Safety and efficacy study of umbilical cord/placenta-derived mesenchymal stem cells to treat myelodysplastic syndromes
UCB-MSCs	Stem cell therapy for type 1 diabetes mellitus
UCB-MSCs	Study to compare the efficacy and safety of cartistem® and microfracture in patients with knee articular cartilage injury or defect
UC-MSCs	A research study looking at specific tissue of the umbilical cord
UC-MSCs	Allogeneic mesenchymal stem cell for Graft-versus-host disease treatment
UC-MSCs/Placenta-MSCs	Safety and efficacy study of umbilical cord/placenta-derived mesenchymal stem cells to treat myelodysplastic syndromes
Placenta-MSCs	Safety of intramuscular injection of Allogeneic PLX-PAD cells for the treatment of critical limb ischemia
UCB-MSCs	Successful stem cell therapy using umbilical cord blood-derived multipotent stem cells for Buerger's disease and ischemic limb disease animal model[103]
UCB-MSCs	A 37-year-old spinal cord-injured female patient, transplanted of multipotent stem cells from human UC blood, with improved sensory perception and mobility, both functionally and morphologically: a case study[104]

Table 3 Differentiation potential of perinatal mesenchymal stromal cells

Mesoderm		Endoderm		Ectoderm
Bone	[74,75,105-109]	Skin, skin epithelium	[110]	Lung, respiratory epithelium	[111,112]
Cartilage	[76,113,114]	Nerve, neuronal, glial	[64,115-124]	Liver, hepatocytes	[125-128]
Adipose tissue	[48,49,51,129]			Islets, beta cells	[130,131]
Skeletal muscle	[54,132-136]
Cardiac muscle	[77,137-142]
Vessels, Endothelium	[116,129,143-145]
Stromal support	[79,81,82,146,147]
Immune regulation	[83,148-151]

Some refrences-if highly interesting or comparing mesenchymal stromal cells (MSCs) from different tissues- refer toin vitrodata. This list can by no means be regarded as comprehensive. It shall just give an overview on the broad (pre)clinical potential of MSCs.