title: Improved cell survival and paracrine capacity of human embryonic stem cell-derived mesenchymal stem cells promote therapeutic potential for pulmonary arterial hypertension.
abstract: Although transplantation of adult bone marrow mesenchymal stem cells (BM-MSCs) holds promise in the treatment for pulmonary arterial hypertension (PAH), the poor survival and differentiation potential of adult BM-MSCs have limited their therapeutic efficiency. Here, we compared the therapeutic efficacy of human embryonic stem cell-derived MSCs (hESC-MSCs) with adult BM-MSCs for the treatment of PAH in an animal model. One week following monocrotaline (MCT)-induced PAH, mice were randomly assigned to receive phosphate-buffered saline (MCT group); 3.0×10(6) human BM-derived MSCs (BM-MSCs group) or 3.0×10(6) hESC-derived MSCs (hESC-MSCs group) via tail vein injection. At 3 weeks post-transplantation, the right ventricular systolic pressure (RVSP), degree of RV hypertrophy, and medial wall thickening of pulmonary arteries were lower=, and pulmonary capillary density was higher in the hESC-MSC group as compared with BM-MSC and MCT groups (all p < 0.05). At 1 week post-transplantation, the number of engrafted MSCs in the lungs was found significantly higher in the hESC-MSC group than in the BM-MSC group (all p < 0.01). At 3 weeks post-transplantation, implanted BM-MSCs were undetectable whereas hESC-MSCs were not only engrafted in injured pulmonary arteries but had also undergone endothelial differentiation. In addition, protein profiling of hESC-MSC- and BM-MSC-conditioned medium revealed a differential paracrine capacity. Classification of these factors into bioprocesses revealed that secreted factors from hESC-MSCs were preferentially involved in early embryonic development and tissue differentiation, especially blood vessel morphogenesis. We concluded that improved cell survival and paracrine capacity of hESC-MSCs provide better therapeutic efficacy than BM-MSCs in the treatment for PAH.
authors: Cardiology Division, Department of Medicine, University of Hong Kong, Hong Kong.
authors: Yuelin
authors: Y
authors: Zhang
authors: Songyan
authors: S
authors: Liao
authors: Mo
authors: M
authors: Yang
authors: Xiaoting
authors: X
authors: Liang
authors: Ming-Wai
authors: MW
authors: Poon
authors: Chee-Yin
authors: CY
authors: Wong
authors: Junwen
authors: J
authors: Wang
authors: Zhongjun
authors: Z
authors: Zhou
authors: Soon-Keng
authors: SK
authors: Cheong
authors: Chuen-Neng
authors: CN
authors: Lee
authors: Hung-Fat
authors: HF
authors: Tse
authors: Qizhou
authors: Q
authors: Lian
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D065627:Familial Primary Pulmonary Hypertension; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID