Derivation and characterization of human fetal MSCs: an alternative cell source for large-scale production of cardioprotective microparticles.
The therapeutic effects of mesenchymal stem cells (MSCs) transplantation are increasingly thought to be mediated by MSC secretion. We have previously demonstrated that human ESC-derived MSCs (hESC-MSCs) produce cardioprotective microparticles in pig model of myocardial ischemia/reperfusion (MI/R) injury. As the safety and availability of clinical grade human ESCs remain a concern, MSCs from fetal tissue sources were evaluated as alternatives. Here we derived five MSC cultures from limb, kidney and liver tissues of three first trimester aborted fetuses and like our previously described hESC-derived MSCs; they were highly expandable and had similar telomerase activities. Each line has the potential to generate at least 10(16-19) cells or 10(7-10) doses of cardioprotective secretion for a pig model of MI/R injury. Unlike previously described fetal MSCs, they did not express pluripotency-associated markers such as Oct4, Nanog or Tra1-60. They displayed a typical MSC surface antigen profile and differentiated into adipocytes, osteocytes and chondrocytes in vitro. Global gene expression analysis by microarray and qRT-PCR revealed a typical MSC gene expression profile that was highly correlated among the five fetal MSC cultures and with that of hESC-MSCs (r(2)>0.90). Like hESC-MSCs, they produced secretion that was cardioprotective in a mouse model of MI/R injury. HPLC analysis of the secretion revealed the presence of a population of microparticles with a hydrodynamic radius of 50-65 nm. This purified population of microparticles was cardioprotective at approximately 1/10 dosage of the crude secretion.
Lai
Ruenn Chai
RC
Institute of Medical Biology, Agency for Science Technology and Research (ASTAR), Singapore.
Arslan
Fatih
F
Tan
Soon Sim
SS
Tan
Betty
B
Choo
Andre
A
Lee
May May
MM
Chen
Tian Sheng
TS
Teh
Bao Ju
BJ
Eng
John Kun Long
JK
Sidik
Harwin
H
Tanavde
Vivek
V
Hwang
Wei Sek
WS
Lee
Chuen Neng
CN
El Oakley
Reida Menshawe
RM
Pasterkamp
Gerard
G
de Kleijn
Dominique P V
DP
Tan
Kok Hian
KH
Lim
Sai Kiang
SK
D000818:Animals; D000941:Antigens / Q000737:chemistry; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D053595:Embryonic Stem Cells / Q000166:cytology*; D020869:Gene Expression Profiling; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008863:Microspheres; D020411:Oligonucleotide Array Sequence Analysis; D010316:Particle Size; D015427:Reperfusion Injury / Q000473:pathology; D013552:Swine; D014018:Tissue Distribution
D000941:Antigens