Patient-specific cardiovascular progenitor cells derived from integration-free induced pluripotent stem cells for vascular tissue regeneration

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• 作者：Jiang Hu^a ; ¹ ; Yongyu Wang^b ; ¹ ; Jiao Jiao^b ; Zhongning Liu^a ; ^c ; Chao Zhao^a ; Zhou Zhou^b ; Zhanpeng Zhang^d ; Kaitlynn Forde^a ; Lunchang Wang^b ; Jiangang Wang^b ; ^e ; David J. Baylink^f ; Xiao-Bing Zhang^f ; Shaorong Gao^g ; Bo Yang^b ; ^{boya@umich.edu" class="auth_mail" title="E-mail the corresponding author} ; Y. Eugene Chen^b ; ^{echenum@umich.edu" class="auth_mail" title="E-mail the corresponding author} ; Peter X. Ma^a ; ^d ; ^h ; ⁱ ; ^{mapx@umich.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Human induced pluripotent stem cell ; Cardiovascular progenitor cell ; Vascular smooth muscle cell ; Macroporous nanofibrous scaffold ; Tissue-engineered vascular tissue
• 刊名：Biomaterials
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：73
• 期：Complete
• 页码：51-59
• 全文大小：2805 K

文摘

Tissue-engineered blood vessels (TEBVs) are promising in regenerating a live vascular replacement. However, the vascular cell source is limited, and it is crucial to develop a scaffold that accommodates new type of vascular progenitor cells and facilitates in vivo lineage specification of the cells into functional vascular smooth muscle cells (VSMCs) to regenerate vascular tissue. In the present study, integration-free human induced pluripotent stem cells (hiPSCs) were established from patient peripheral blood mononuclear cells through episomal vector nucleofection of reprogramming factors. The established hiPSCs were then induced into mesoderm-originated cardiovascular progenitor cells (CVPCs) with a highly efficient directed lineage specification method. The derived CVPCs were demonstrated to be able to differentiate into functional VSMCs. Subcutaneous implantation of CVPCs seeded on macroporous nanofibrous poly(l-lactide) scaffolds led to in vivo VSMC lineage specification and matrix deposition inside the scaffolds. In summary, we established integration-free patient-specific hiPSCs from peripheral blood mononuclear cells, derived CVPCs through directed lineage specification, and developed an advanced scaffold for these progenitor cells to further differentiate in vivo into VSMCs and regenerate vascular tissue in a subcutaneous implantation model. This study has established an efficient patient-specific approach towards in vivo regeneration of vascular tissue.