Comparative analysis of mesenchymal stem/stromal cells derived from human induced pluripotent stem cells and the cognate umbilical cord mesenchymal stem/stromal cells
Quanlei Wang,
Yuwei Wang,
Chongfei Chang,
Feilong Ma,
Dongxiu Peng,
Shun Yang,
Yanru An,
Qiuting Deng,
Qixiao Wang,
Fei Gao,
Fei Wang,
Huiru Tang,
Xufeng Qi,
Xiaoming Jiang,
Dongqing Cai,
Guangqian Zhou
Affiliations
Quanlei Wang
Key Laboratory of Regenerative Medicine of Ministry of Education, Biology Postdoctoral Research Station, Jinan University, Guangzhou, China; Cheerland Danlun Biopharma Co. Ltd., Dapeng New District, Shenzhen, China; Department of Medical Cell Biology and Genetics, Guangdong Key Laboratory of Genomic Stability and Disease Prevention, Shenzhen Key Laboratory of Anti-Aging and Regenerative Medicine, and Shenzhen Engineering Laboratory of Regenerative Technologies for Orthopaedic Diseases, Health Science Center, Shenzhen University, Shenzhen, China
Yuwei Wang
Cheerland Danlun Biopharma Co. Ltd., Dapeng New District, Shenzhen, China; The SZU-Cheerland Institute for Advanced and Innovative Medicine, Shenzhen, China
Chongfei Chang
Cheerland Danlun Biopharma Co. Ltd., Dapeng New District, Shenzhen, China
Feilong Ma
Cheerland Danlun Biopharma Co. Ltd., Dapeng New District, Shenzhen, China
Dongxiu Peng
Cheerland Danlun Biopharma Co. Ltd., Dapeng New District, Shenzhen, China
Shun Yang
Cheerland Danlun Biopharma Co. Ltd., Dapeng New District, Shenzhen, China
Yanru An
BGI-Shenzhen, Shenzhen, China
Qiuting Deng
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
Qixiao Wang
Department of Oral and Maxillofacial Surgery, The First People's Hospital of Huaihua, University of South China, Huaihua, Hunan, China
Fei Gao
China Food and Drug Administration, Beijing, China
Fei Wang
The SZU-Cheerland Institute for Advanced and Innovative Medicine, Shenzhen, China
Huiru Tang
Cheerland Danlun Biopharma Co. Ltd., Dapeng New District, Shenzhen, China
Xufeng Qi
Key Laboratory of Regenerative Medicine of Ministry of Education, Biology Postdoctoral Research Station, Jinan University, Guangzhou, China
Xiaoming Jiang
The SZU-Cheerland Institute for Advanced and Innovative Medicine, Shenzhen, China; Corresponding author. The SZU-Cheerland Institute for Advanced and Innovative Medicine, Shenzhen, China.
Dongqing Cai
Key Laboratory of Regenerative Medicine of Ministry of Education, Biology Postdoctoral Research Station, Jinan University, Guangzhou, China; Corresponding author. Key Laboratory of Regenerative Medicine of Ministry of Education, Biology Postdoctoral Research Station, Jinan University, Guangzhou, China.
Guangqian Zhou
Cheerland Danlun Biopharma Co. Ltd., Dapeng New District, Shenzhen, China; Department of Medical Cell Biology and Genetics, Guangdong Key Laboratory of Genomic Stability and Disease Prevention, Shenzhen Key Laboratory of Anti-Aging and Regenerative Medicine, and Shenzhen Engineering Laboratory of Regenerative Technologies for Orthopaedic Diseases, Health Science Center, Shenzhen University, Shenzhen, China; The SZU-Cheerland Institute for Advanced and Innovative Medicine, Shenzhen, China; Corresponding author. The SZU-Cheerland Institute for Advanced and Innovative Medicine, Shenzhen, China.
Mesenchymal stem/stromal cells (MSCs) show tremendous potential for regenerative medicine due to their self-renewal, multi-differentiation and immunomodulatory capabilities. Largely studies had indicated conventional tissue-derived MSCs have considerable limited expandability and donor variability which hinders further application. Induced pluripotent stem cell (iPSCs)-derived MSCs (iMSCs) have created exciting source for standardized cellular therapy. However, the cellular and molecular differences between iMSCs and the cognate tissue-derived MSCs remains poorly explored. In this study, we first successfully reprogrammed human umbilical cords-derived mesenchymal stem/stromal cells (UMSCs) into iPSCs by using the cocktails of mRNA. Subsequently, iPSCs were further differentiated into iMSCs in xeno-free induction medium. Then, iMSCs were compared with the donor matched UMSCs by assessing proliferative state, differentiation capability, immunomodulatory potential through immunohistochemical analysis, flow cytometric analysis, transcriptome sequencing analysis, and combine with coculture with immune cell population. The results showed that iMSCs exhibited high expression of MSCs positive-makers CD73, CD90, CD105 and lack expression of negative-maker cocktails CD34, CD45, CD11b, CD19, HLA-DR; also successfully differentiated into osteocytes, chondrocytes and adipocytes. Further, the iMSCs were similar with their parental UMSCs in cell proliferative state detected by the CCK-8 assay, and in cell rejuvenation state assessed by β-Galactosidase staining and telomerase activity related mRNA and protein analysis. However, iMSCs exhibited similarity to resident MSCs in Homeobox (Hox) genes expression profile and presented better neural differentiation potential by activation of NESTIN related pathway. Moreover, iMSCs owned enhanced immunosuppression capacity through downregulation pools of pro-inflammatory factors, including IL6, IL1B etc. and upregulation anti-inflammatory factors NOS1, TGFB etc. signals. In summary, our study provides an attractive cell source for basic research and offers fundamental biological insight of iMSCs-based therapy.
