Improved cell survival and paracrine capacity of human embryonic stem cell-derived mesenchymal stem cells promote therapeutic potential for pulmonary arterial hypertension.
Cell Transplant
; 21(10): 2225-39, 2012.
Article
en En
| MEDLINE
| ID: mdl-22776744
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Trasplante de Células Madre Mesenquimatosas
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Células Madre Embrionarias
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Células Madre Mesenquimatosas
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Hipertensión Pulmonar
Tipo de estudio:
Clinical_trials
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Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
Cell Transplant
Asunto de la revista:
TRANSPLANTE
Año:
2012
Tipo del documento:
Article
País de afiliación:
Hong Kong