PDGFB-expressing mesenchymal stem cells improve human hematopoietic stem cell engraftment in immunodeficient mice.,Bone Marrow Transplantation

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PDGFB-expressing mesenchymal stem cells improve human hematopoietic stem cell engraftment in immunodeficient mice.
Bone Marrow Transplantation ( IF 4.5 ) Pub Date : 2019-12-05 , DOI: 10.1038/s41409-019-0766-z
Xiuxiu Yin ₁ , Linping Hu ₁ , Yawen Zhang ₁ , Caiying Zhu ₁ , Hui Cheng ₁ , Xiaowei Xie ₁ , Ming Shi ₁ , Ping Zhu ₁ , Xueying Zhao ₁ , Wanqiu Chen ₂ , Lu Zhang ₁ , Cameron Arakaki ₂ , Sha Hao ₁ , Mei Wang ₁ , Wenbin Cao ₁ , Shihui Ma ₁ , Xiao-Bing Zhang _{1,

2} , Tao Cheng _{1,

3}

Affiliation

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.

中文翻译：

表达 PDGFB 的间充质干细胞可改善免疫缺陷小鼠的人类造血干细胞移植。

骨髓 (BM) 生态位调节多个造血干细胞 (HSC) 过程。通过 HSC 移植治疗血液系统恶性肿瘤通常需要通过全身照射进行预处理，这会严重且不可逆转地损害 BM 生态位和 HSC 再生。需要新的策略来增强辐照 BM 中的 HSC 再生。我们使用通过慢病毒载体转导这些因子的人类间充质干细胞 (MSC)，比较了 EGF、FGF2 和 PDGFB 对 HSC 再生的影响。在上述测试的生态位因子中，用 PDGFB (PDGFB-MSC) 转导的 MSC 最显着地改善了免疫缺陷小鼠中的人类 HSC 植入。PDGFB-MSC 处理的 BM 比 GFP 转导的 MSC (GFP-MSC) 更有效地增强了移植的人类 HSC 在二次移植中的自我更新。基因集富集分析显示，与 GFP-MSCs 相比，PDGFB-MSCs 中的抗凋亡信号增加。PDGFB-MSCs 在移植后表现出增强的存活和扩增，导致扩大的人源化生态位细胞库，提供更好的人源化微环境，以促进人类造血细胞的卓越植入和增殖。我们的研究证明了 PDGFB-MSCs 在支持人类 HSC 移植方面的功效。

更新日期：2019-12-05

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