Changsun Lee1, Sehwan Shim2, Hyosun Jang2, Hyunwook Myung1, Janet Lee2, Chang-Hwan Bae2, Jae Kyung Myung3, Min-Jung Kim2, Seung Bum Lee2, Won-Suk Jang2, Sun-Joo Lee2, Hwi-Yool Kim4, Seung-Sook Lee3, Sunhoo Park5. 1. Laboratory of Radiation Exposure and Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea; Department of Veterinary Surgery, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea. 2. Laboratory of Radiation Exposure and Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea. 3. Laboratory of Radiation Exposure and Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea; Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea. 4. Department of Veterinary Surgery, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea. 5. Laboratory of Radiation Exposure and Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea; Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea. Electronic address: sunhoo@kcch.re.kr.
Abstract
BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) are a promising agent for treating impaired wound healing, and their therapeutic potential may be enhanced by employing extracellular matrix scaffolds as cell culture scaffolds or transplant cell carriers. Here, we evaluated the effect of human umbilical cord blood-derived (hUCB)-MSCs and a porcine small intestinal submucosa (SIS)-derived extracellular matrix scaffold in a combined radiation-wound mouse model of impaired wound healing. METHODS: hUCB-MSCs and SIS hydrogel composite was applied to the excisional wound of whole-body irradiated mice. Assessment of wound closing and histological evaluation were performed in vivo. We also cultured hUCB-MSCs on SIS gel and examined the angiogenic effect of conditioned medium on irradiated human umbilical vein endothelial cells (HUVECs) in vitro. RESULTS: hUCB-MSCs and SIS hydrogel composite treatment enhanced wound healing and angiogenesis in the wound site of mice. Conditioned medium from hUCB-MSCs cultured on SIS hydrogel promoted the chemotaxis of irradiated HUVECs more than their proliferation. The secretion of angiogenic growth factors hepatocyte growth factor, vascular endothelial growth factor-A and angiopoietin-1 from hUCB-MSCs was significantly increased by SIS hydrogel, with HGF being the predominant angiogenic factor of irradiated HUVECs. CONCLUSIONS: Our results suggest that the wound healing effect of hUCB-MSCs is enhanced by SIS hydrogel via a paracrine factor-mediated recruitment of vascular endothelial cells in a combined radiation-wound mouse model.
BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) are a promising agent for treating impaired wound healing, and their therapeutic potential may be enhanced by employing extracellular matrix scaffolds as cell culture scaffolds or transplant cell carriers. Here, we evaluated the effect of human umbilical cord blood-derived (hUCB)-MSCs and a porcine small intestinal submucosa (SIS)-derived extracellular matrix scaffold in a combined radiation-wound mouse model of impaired wound healing. METHODS: hUCB-MSCs and SIS hydrogel composite was applied to the excisional wound of whole-body irradiated mice. Assessment of wound closing and histological evaluation were performed in vivo. We also cultured hUCB-MSCs on SIS gel and examined the angiogenic effect of conditioned medium on irradiated human umbilical vein endothelial cells (HUVECs) in vitro. RESULTS: hUCB-MSCs and SIS hydrogel composite treatment enhanced wound healing and angiogenesis in the wound site of mice. Conditioned medium from hUCB-MSCs cultured on SIS hydrogel promoted the chemotaxis of irradiated HUVECs more than their proliferation. The secretion of angiogenic growth factors hepatocyte growth factor, vascular endothelial growth factor-A and angiopoietin-1 from hUCB-MSCs was significantly increased by SIS hydrogel, with HGF being the predominant angiogenic factor of irradiated HUVECs. CONCLUSIONS: Our results suggest that the wound healing effect of hUCB-MSCs is enhanced by SIS hydrogel via a paracrine factor-mediated recruitment of vascular endothelial cells in a combined radiation-wound mouse model.
Authors: Siufui Hendrawan; Yuyus Kusnadi; Christine Ayu Lagonda; Dilafitria Fauza; Jennifer Lheman; Erwin Budi; Brian Saputra Manurung; Hans Ulrich Baer; Sukmawati Tansil Tan Journal: Vet World Date: 2021-08-17
Authors: Raghavan Chinnadurai; Paul D Bates; Keith A Kunugi; Kwangok P Nickel; Larry A DeWerd; Christian M Capitini; Jacques Galipeau; Randall J Kimple Journal: Front Immunol Date: 2021-07-26 Impact factor: 7.561