Lung Disease - Mesenchymal Stem Cells

Improved Cell Survival and Paracrine Capacity of Human Embryonic Stem Cell-derived Mesenchymal Stem Cells Promote Therapeutic Potential for Pulmonary Arterial Hypertension

Yuelin Zhang,* Songyan Liao,* Mo Yang,†‡ Xiaoting Liang,* Ming-Wai Poon,* Chee-Yin Wong,§ Junwen Wang,¶ Zhongjun Zhou,¶ Soon-Keng Cheong,§ Chuen-Neng Lee,# Hung-Fat Tse,*,** and Qizhou Lian*,**†† 

*Cardiology Division, Department of Medicine, University of Hong Kong, Hong Kong. †Southern Medical University, ‡Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong §MAKNA-HUKM Cancer Research Institute, Kuala Lumpur, ¶Department of Biochemistry, University of Hong Kong, Hong Kong. #National University of Singapore, Singapore. **Research Centre of Heart, Brain, Hormone, and Healthy Aging, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong. ††Eye Institute, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong. 

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.