BACKGROUND AIMS: Stem cells have been shown to have a therapeutic effect in several ischemic animal models, including hindlimb ischemia and chronic wound. We examined the wound-healing effect of secretory factors released by human embryonic stem cell (hESC)-derived endothelial precursor cells (EPC) in cutaneous excisional wound models. METHODS: hESC-EPC were sorted by CD133/KDR, and endothelial characteristics were confirmed by reverse transcription (RT)-polymerase chain reaction (PCR), Matrigel assay and ac-LDL uptake. Conditioned medium (CM) of hESC-EPC was prepared, and concentrated hESC-EPC CM was applied in a mouse excisional wound model. RESULTS: hESC-EPC CM accelerated wound healing and increased the tensile strength of wounds after topical treatment and subcutaneous injection. In addition, hESC-EPC CM treatment caused more rapid re-formation of granulation tissue and re-epithelialization of wounds compared with control vehicle medium and CB-EPC CM-treated wounds. In vitro, hESC-EPC CM significantly improved the proliferation and migration of dermal fibroblasts and epidermal keratinocytes. hESC-EPC CM also increased the extracellular matrix synthesis of fibroblasts. Analysis of hESC-EPC CM with a multiplex cytokine array system indicated that hESC-EPC secreted distinctively different cytokines and chemokines, such as epidermal growth factor (EGF), fibroblast growth factor (bFGF), fractalkine, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, IL-8, platelet-derived growth factor-AA (PDGF-AA) and vascular endothelial growth factor (VEGF), which are well known to be important in normal angiogenesis and wound healing. CONCLUSIONS: This study has demonstrated the wound-healing effect of hESC-EPC CM and characterized the spectrum of cytokines released by hESC-EPC that are functionally involved in the wound-healing process. These results suggest that secretory factors released from stem cells could be an important mediator of stem cell therapy in ischemic tissue diseases.
BACKGROUND AIMS: Stem cells have been shown to have a therapeutic effect in several ischemic animal models, including hindlimb ischemia and chronic wound. We examined the wound-healing effect of secretory factors released by human embryonic stem cell (hESC)-derived endothelial precursor cells (EPC) in cutaneous excisional wound models. METHODS: hESC-EPC were sorted by CD133/KDR, and endothelial characteristics were confirmed by reverse transcription (RT)-polymerase chain reaction (PCR), Matrigel assay and ac-LDL uptake. Conditioned medium (CM) of hESC-EPC was prepared, and concentrated hESC-EPC CM was applied in a mouse excisional wound model. RESULTS: hESC-EPC CM accelerated wound healing and increased the tensile strength of wounds after topical treatment and subcutaneous injection. In addition, hESC-EPC CM treatment caused more rapid re-formation of granulation tissue and re-epithelialization of wounds compared with control vehicle medium and CB-EPC CM-treated wounds. In vitro, hESC-EPC CM significantly improved the proliferation and migration of dermal fibroblasts and epidermal keratinocytes. hESC-EPC CM also increased the extracellular matrix synthesis of fibroblasts. Analysis of hESC-EPC CM with a multiplex cytokine array system indicated that hESC-EPC secreted distinctively different cytokines and chemokines, such as epidermal growth factor (EGF), fibroblast growth factor (bFGF), fractalkine, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, IL-8, platelet-derived growth factor-AA (PDGF-AA) and vascular endothelial growth factor (VEGF), which are well known to be important in normal angiogenesis and wound healing. CONCLUSIONS: This study has demonstrated the wound-healing effect of hESC-EPC CM and characterized the spectrum of cytokines released by hESC-EPC that are functionally involved in the wound-healing process. These results suggest that secretory factors released from stem cells could be an important mediator of stem cell therapy in ischemic tissue diseases.
Authors: Anna Grochot-Przeczek; Jerzy Kotlinowski; Magdalena Kozakowska; Katarzyna Starowicz; Jolanta Jagodzinska; Anna Stachurska; Oscar L Volger; Karolina Bukowska-Strakova; Urszula Florczyk; Magdalena Tertil; Agnieszka Jazwa; Krzysztof Szade; Jacek Stepniewski; Agnieszka Loboda; Anton J G Horrevoets; Jozef Dulak; Alicja Jozkowicz Journal: Antioxid Redox Signal Date: 2014-02-28 Impact factor: 8.401
Authors: Bruno Amato; Rita Compagna; Maurizio Amato; Lucia Butrico; Francesco Fugetto; Mariia D Chibireva; Andrea Barbetta; Marco Cannistrà; Stefano de Franciscis; Raffaele Serra Journal: Int Wound J Date: 2015-09-24 Impact factor: 3.315
Authors: Sundeep G Keswani; Swathi Balaji; Louis D Le; Alice Leung; Jignesh K Parvadia; Jason Frischer; Seiichi Yamano; Norton Taichman; Timothy M Crombleholme Journal: Wound Repair Regen Date: 2013-06-11 Impact factor: 3.617
Authors: A Kaupisch; L Kennedy; V Stelmanis; B Tye; N M Kane; J C Mountford; A Courtney; A H Baker Journal: J Cardiovasc Transl Res Date: 2012-08-02 Impact factor: 4.132