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Relative contributions of adipose-resident CD146+ pericytes and CD34+ adventitial progenitor cells in bone tissue engineering.

ABSTRACT: Pericytes and other perivascular stem/stromal cells are of growing interest in the field of tissue engineering. A portion of perivascular cells are well recognized to have MSC (mesenchymal stem cell) characteristics, including multipotentiality, self-renewal, immunoregulatory functions, and diverse roles in tissue repair. Here, we investigate the differential but overlapping roles of two perivascular cell subsets in paracrine induction of bone repair. CD146+CD34-CD31-CD45-pericytes and CD34+CD146-CD31-CD45-adventitial cells were derived from human adipose tissue and applied alone or in combination to calvarial bone defects in mice. In vitro, osteogenic differentiation and tubulogenesis assays were performed using either fluorescence activated cell sorting-derived CD146+ pericytes or CD34+ adventitial cells. Results showed that CD146+ pericytes induced increased cord formation in vitro and angiogenesis in vivo in comparison with patient-matched CD34+ adventitial cells. In contrast, CD34+ adventitial cells demonstrated heightened paracrine-induced osteogenesis in vitro. When applied in a critical-size calvarial defect model in NOD/SCID mice, the combination treatment of CD146+ pericytes with CD34+ adventitial cells led to greater re-ossification than either cell type alone. In summary, adipose-derived CD146+ pericytes and CD34+ adventitial cells display functionally distinct yet overlapping and complementary roles in bone defect repair. Consequently, CD146+ pericytes and CD34+ adventitial cells may demonstrate synergistic bone healing when applied as a combination cellular therapy.

SUBMITTER: Wang Y

PROVIDER: S-EPMC6323123 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Relative contributions of adipose-resident CD146+ pericytes and CD34+ adventitial progenitor cells in bone tissue engineering.

Wang Yiyun Y Xu Jiajia J Chang Leslie L Meyers Carolyn A CA Zhang Lei L Broderick Kristen K Lee Min M Peault Bruno B James Aaron W AW

NPJ Regenerative medicine 20190107

Pericytes and other perivascular stem/stromal cells are of growing interest in the field of tissue engineering. A portion of perivascular cells are well recognized to have MSC (mesenchymal stem cell) characteristics, including multipotentiality, self-renewal, immunoregulatory functions, and diverse roles in tissue repair. Here, we investigate the differential but overlapping roles of two perivascular cell subsets in paracrine induction of bone repair. CD146+CD34-CD31-< ...[more]

PMID: 30622740

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Project description:BACKGROUND:To date, many attempts are employed to increase the regenerative potential of stem cells. In this study, we evaluated the hypothesis of whether an autophagy modulation could alter differentiation potency of CD146+ cells into mature pericyte, endothelial, and cardiomyocyte lineage. METHODS:In this study, CD146+cells were enriched from the human bone marrow aspirates and trans-differentiated into mature endothelial cells, pericytes, and cardiomyocytes after exposure to autophagy stimulator (50-?M Met)/inhibitor (15-?M HCQ). The protein levels of autophagy proteins were monitored by western blotting. NO content was measured using the Griess assay. Using real-time PCR assay and western blotting, we monitored the lineage protein and gene levels. Pro-inflammatory cytokine and angiocrine factors were measured by ELISA. The fatty acid change was determined by gas chromatography. We also measured exosome secretion capacity by measuring AChE activity and real-time PCR assay. RESULT:Data revealed the modulation of autophagy factors, Beclin-1, P62, and LC3 II/I ratio in differentiating CD146+ cells after exposure to Met and HCQ (p?<?0.05). The inhibition of autophagy increased NO content compared to the Met-treated cells (p?<?0.05). Real-time PCR analysis showed that the treatment of CD146+ cells with autophagy modulators altered the expression of VE-cadherin, cTnI, and ?-SMA (p?<?0.05). Met increased the expression of VE-cadherin, ?-SMA, and cTnI compared to the HCQ-treated cells (p?<?0.05) while western blotting revealed the protein synthesis of all lineage-specific proteins under the stimulation and inhibition of autophagy. None statistically significant differences were found in the levels of Tie-1, Tie-2, VEGFR-1, and VEGFR-2 after autophagy modulation. Fatty acid profile analysis revealed the increase of unsaturated fatty acids after exposure to HCQ (p?<?0.05). The treatment of cells with HCQ increased the levels of TNF-? and IL-6 compared to the Met-treated cells. Data revealed the increase of exosome biogenesis and secretion to the supernatant in cells treated with HCQ compared to the Met groups (p?<?0.05). CONCLUSIONS:In summary, autophagy modulation could alter differentiation potency of CD146+cells which is important in cardiac regeneration.

Dataset Information

Relative contributions of adipose-resident CD146+ pericytes and CD34+ adventitial progenitor cells in bone tissue engineering.

Publications

Relative contributions of adipose-resident CD146<sup>+</sup> pericytes and CD34<sup>+</sup> adventitial progenitor cells in bone tissue engineering.

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