title: Patient-specific cardiovascular progenitor cells derived from integration-free induced pluripotent stem cells for vascular tissue regeneration.
abstract: 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.
authors.affiliation: Department of Biologic and Materials Sciences, The University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Yongyu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Jiao
authors.initials: J
authors.lastname: Jiao
authors.affiliation: Department of Biologic and Materials Sciences, The University of Michigan, Ann Arbor, MI 48109, USA; Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.
authors.forename: Zhongning
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Biologic and Materials Sciences, The University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Biomedical Engineering, The University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Zhanpeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Biologic and Materials Sciences, The University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Kaitlynn
authors.initials: K
authors.lastname: Forde
authors.affiliation: Department of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Lunchang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan, Ann Arbor, MI 48109, USA; Department of Cardiac Surgery, Beijing Anzhen Hospitial, Capital Medical University, Beijing 100029, China.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Baylink
authors.affiliation: Department of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Zhang
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Shaorong
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: boya@umich.edu.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: echenum@umich.edu.
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
authors.affiliation: Department of Biologic and Materials Sciences, The University of Michigan, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, The University of Michigan, Ann Arbor, MI 48109, USA; Macromolecular Science and Engineering Center, The University of Michigan, Ann Arbor, MI 48109, USA; Department of Materials Science and Engineering, The University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: mapx@umich.edu.
authors.forename: Peter X
authors.initials: PX
authors.lastname: Ma
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001011:Aorta / Q000473:pathology; D001807:Blood Vessel Prosthesis; D002454:Cell Differentiation; D019070:Cell Lineage; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008648:Mesoderm; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009200:Myocardial Contraction; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000166:cytology; D011091:Polyesters / Q000737:chemistry; D016062:Porosity; D012038:Regeneration; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D018952:Antigens, CD34; D011091:Polyesters; C033616:poly(lactide)
keywords: Cardiovascular progenitor cell; Human induced pluripotent stem cell; Macroporous nanofibrous scaffold; Tissue-engineered vascular tissue; Vascular smooth muscle cell