TY - JOUR
T1 - Adipose-derived stem cell induced-tissue repair or wound healing is mediated by the concomitant upregulation of miR-21 and miR-29b expression and activation of the AKT signaling pathway
AU - Liu, Shao Cheng
AU - Bamodu, Oluwaseun Adebayo
AU - Kuo, Kuang Tai
AU - Fong, Iat Hang
AU - Lin, Chih Cheng
AU - Yeh, Chi Tai
AU - Chen, Shyi Gen
N1 - Funding Information:
This work was supported by the National Science Council of Taiwan grant to Shyi-Gen Chen ( MOST 109-2314-B-016-007 -) and Shao-Cheng Liu ( MOST 108-2314-B-016 -040 -MY3 ). This study was also supported by grants from and Tri-Service General Hospital ( TSGH-D-109139 and MND-MAB-D-111116 ) to Shyi-Gen Chen and Shao-Cheng Liu ( TSGH-D-109054 and TSGH-D-110080 ).
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/7/15
Y1 - 2021/7/15
N2 - Background: Adipose-derived stem cells (ADSCs), a subpopulation of mesenchymal stem cells, are characterized by their potential to differentiate into multiple cell lineages. Due to their abundance and relative ease of procurement, ADSCs are widely used for tissue repair and regeneration. However, the molecular mechanisms of the therapeutic effect of ADSCs remain unknown. Methods: MicroRNAs have emerged as important signaling molecules in skin wound healing, and their roles in ADSC-based therapies must be addressed. Here, we investigated the potential of ADSCs in improving cutaneous wound healing in vitro and in vivo. Results: We simulated the microenvironment of the wound site by coculturing human dermal fibroblasts (HDFs) with ADSCs. We found that cocultured HDFs expressed significantly higher levels of miR-29b and miR-21 and had higher proliferation and migration rates than ADSCs cultured without HDFs. Moreover, increased expression of Collagen Type I Alpha 1 Chain (COL1A1), Collagen Type III Alpha 1 Chain (COL3A1), alpha-smooth muscle actin (α-SMA), vascular endothelial growth factor (VEGF), and Phosphoinositide 3-kinase (PI3K), p-Akt and decreased expression of Phosphatase and tensin homolog (PTEN) and matrix metalloproteinase (MMP)-1 was detected, suggesting extracellular remodeling and fibroblast activation and proliferation. We validated the in vitro results by using a rodent skin excisional wound model and implanted ADSC sheets in the wound. Compared with the controls, wounds implanted with ADSC sheets had significantly higher rates of wound-closure; increased expression of α-SMA, VEGF, PI3k, PTEN, COL1A1, and COL3A1; decreased expression of PTEN and MMP1; and upregulated levels of miR-29b and miR-21 in the skin. Conclusion: In summary, we evidenced that ADSCs facilitate the increase in miR-29b and miR-21 levels and promote the activation and proliferation of dermal fibroblasts and extracellular matrix (ECM) remodeling, with the associated release of VEGF. Thus, the ADSC-mediated increase in microRNAs is essential in tissue repair and has a therapeutic potential in cutaneous wound healing.
AB - Background: Adipose-derived stem cells (ADSCs), a subpopulation of mesenchymal stem cells, are characterized by their potential to differentiate into multiple cell lineages. Due to their abundance and relative ease of procurement, ADSCs are widely used for tissue repair and regeneration. However, the molecular mechanisms of the therapeutic effect of ADSCs remain unknown. Methods: MicroRNAs have emerged as important signaling molecules in skin wound healing, and their roles in ADSC-based therapies must be addressed. Here, we investigated the potential of ADSCs in improving cutaneous wound healing in vitro and in vivo. Results: We simulated the microenvironment of the wound site by coculturing human dermal fibroblasts (HDFs) with ADSCs. We found that cocultured HDFs expressed significantly higher levels of miR-29b and miR-21 and had higher proliferation and migration rates than ADSCs cultured without HDFs. Moreover, increased expression of Collagen Type I Alpha 1 Chain (COL1A1), Collagen Type III Alpha 1 Chain (COL3A1), alpha-smooth muscle actin (α-SMA), vascular endothelial growth factor (VEGF), and Phosphoinositide 3-kinase (PI3K), p-Akt and decreased expression of Phosphatase and tensin homolog (PTEN) and matrix metalloproteinase (MMP)-1 was detected, suggesting extracellular remodeling and fibroblast activation and proliferation. We validated the in vitro results by using a rodent skin excisional wound model and implanted ADSC sheets in the wound. Compared with the controls, wounds implanted with ADSC sheets had significantly higher rates of wound-closure; increased expression of α-SMA, VEGF, PI3k, PTEN, COL1A1, and COL3A1; decreased expression of PTEN and MMP1; and upregulated levels of miR-29b and miR-21 in the skin. Conclusion: In summary, we evidenced that ADSCs facilitate the increase in miR-29b and miR-21 levels and promote the activation and proliferation of dermal fibroblasts and extracellular matrix (ECM) remodeling, with the associated release of VEGF. Thus, the ADSC-mediated increase in microRNAs is essential in tissue repair and has a therapeutic potential in cutaneous wound healing.
KW - Activated fibroblasts
KW - Adipose-derived stem cells
KW - AKT signaling
KW - Collagen
KW - MicroRNAs
KW - miR-21
KW - miR-29b
KW - Wound healing
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U2 - 10.1016/j.abb.2021.108895
DO - 10.1016/j.abb.2021.108895
M3 - Article
C2 - 33933426
AN - SCOPUS:85107121986
SN - 0003-9861
VL - 705
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
M1 - 108895
ER -