TY - JOUR
T1 - Keratose Hydrogel Drives Differentiation of Cardiac Vascular Smooth Muscle Progenitor Cells
T2 - Implications in Ischemic Treatment
AU - Ledford, Benjamin T.
AU - Chen, Miao
AU - Van Dyke, Mark
AU - Barron, Catherine
AU - Zhang, Xiaonan
AU - Cartaya, Aurora
AU - Zheng, Youjing
AU - Ceylan, Ahmet
AU - Goldstein, Aaron
AU - He, Jia Qiang
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2023/10
Y1 - 2023/10
N2 - Peripheral artery disease (PAD) is a common vascular disorder in the extremity of limbs with limited clinical treatments. Stem cells hold great promise for the treatment of PAD, but their therapeutic efficiency is limited due to multiple factors, such as poor engraftment and non-optimal selection of cell type. To date, stem cells from a variety of tissue sources have been tested, but little information is available regarding vascular smooth muscle cells (VSMCs) for PAD therapy. The present study examines the effects of keratose (KOS) hydrogels on c-kit+/CD31− cardiac vascular smooth muscle progenitor cell (cVSMPC) differentiation and the therapeutic potential of the resultant VSMCs in a mouse hindlimb ischemic model of PAD. The results demonstrated that KOS but not collagen hydrogel was able to drive the majority of cVSMPCs into functional VSMCs in a defined Knockout serum replacement (SR) medium in the absence of differentiation inducers. This effect could be inhibited by TGF-β1 antagonists. Further, KOS hydrogel increased expression of TGF-β1-associated proteins and modulated the level of free TGF-β1 during differentiation. Finally, transplantation of KOS-driven VSMCs significantly increased blood flow and vascular densities of ischemic hindlimbs. These findings indicate that TGF-β1 signaling is involved in KOS hydrogel-preferred VSMC differentiation and that enhanced blood flow are likely resulted from angiogenesis and/or arteriogenesis induced by transplanted VSMCs. Graphical Abstract: [Figure not available: see fulltext.]
AB - Peripheral artery disease (PAD) is a common vascular disorder in the extremity of limbs with limited clinical treatments. Stem cells hold great promise for the treatment of PAD, but their therapeutic efficiency is limited due to multiple factors, such as poor engraftment and non-optimal selection of cell type. To date, stem cells from a variety of tissue sources have been tested, but little information is available regarding vascular smooth muscle cells (VSMCs) for PAD therapy. The present study examines the effects of keratose (KOS) hydrogels on c-kit+/CD31− cardiac vascular smooth muscle progenitor cell (cVSMPC) differentiation and the therapeutic potential of the resultant VSMCs in a mouse hindlimb ischemic model of PAD. The results demonstrated that KOS but not collagen hydrogel was able to drive the majority of cVSMPCs into functional VSMCs in a defined Knockout serum replacement (SR) medium in the absence of differentiation inducers. This effect could be inhibited by TGF-β1 antagonists. Further, KOS hydrogel increased expression of TGF-β1-associated proteins and modulated the level of free TGF-β1 during differentiation. Finally, transplantation of KOS-driven VSMCs significantly increased blood flow and vascular densities of ischemic hindlimbs. These findings indicate that TGF-β1 signaling is involved in KOS hydrogel-preferred VSMC differentiation and that enhanced blood flow are likely resulted from angiogenesis and/or arteriogenesis induced by transplanted VSMCs. Graphical Abstract: [Figure not available: see fulltext.]
KW - Keratin
KW - Keratose hydrogel
KW - Mouse hindlimb ischemia
KW - TGF-β
KW - Vascular smooth muscle cells
KW - c-kit/CD31 cardiac vascular smooth muscle progenitor cells
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U2 - 10.1007/s12015-023-10574-6
DO - 10.1007/s12015-023-10574-6
M3 - Article
C2 - 37392292
AN - SCOPUS:85163789275
SN - 2629-3269
VL - 19
SP - 2341
EP - 2360
JO - Stem Cell Reviews and Reports
JF - Stem Cell Reviews and Reports
IS - 7
ER -