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MSC endothelial	Inhibition of T cell proliferation	Cells senescence Stable Karyotype Non tumorigenic	[20,32] and own unpublished data[49,61,93,95,96]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.