PDGFB-expressing Mesenchymal Stem Cells Improve Human Hematopoietic Stem Cell Engraftment in Immunodeficient Mice

Overview

Journal Bone Marrow Transplant

Specialty General Surgery

Date 2019 Dec 6

PMID 31804621

Citations 24

Authors

Xiuxiu Yin

Linping Hu

Yawen Zhang

Caiying Zhu

Hui Cheng

Xiaowei Xie

Ming Shi

Ping Zhu

Xueying Zhao

Wanqiu Chen

Lu Zhang

Cameron Arakaki

Sha Hao

Mei Wang

Wenbin Cao

Shihui Ma

Xiao-Bing Zhang

Tao Cheng

Affiliations

Soon will be listed here.

Abstract

The bone marrow (BM) niche regulates multiple hematopoietic stem cell (HSC) processes. Clinical treatment for hematological malignancies by HSC transplantation often requires preconditioning via total body irradiation, which severely and irreversibly impairs the BM niche and HSC regeneration. Novel strategies are needed to enhance HSC regeneration in irradiated BM. We compared the effects of EGF, FGF2, and PDGFB on HSC regeneration using human mesenchymal stem cells (MSCs) that were transduced with these factors via lentiviral vectors. Among the above niche factors tested, MSCs transduced with PDGFB (PDGFB-MSCs) most significantly improved human HSC engraftment in immunodeficient mice. PDGFB-MSC-treated BM enhanced transplanted human HSC self-renewal in secondary transplantations more efficiently than GFP-transduced MSCs (GFP-MSCs). Gene set enrichment analysis showed increased antiapoptotic signaling in PDGFB-MSCs compared with GFP-MSCs. PDGFB-MSCs exhibited enhanced survival and expansion after transplantation, resulting in an enlarged humanized niche cell pool that provide a better humanized microenvironment to facilitate superior engraftment and proliferation of human hematopoietic cells. Our studies demonstrate the efficacy of PDGFB-MSCs in supporting human HSC engraftment.

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