Abstract
BackgroundStem cell therapies have been widely investigated for their healing effects. However, the translation of these therapies has been hampered by the requirement to deliver live allogeneic or autologous cells directly to the wound in a clinical setting. Multipotent adult progenitor cells (MAPC® cells) are a subpopulation of bone marrow-derived adherent stem cells that secrete a wide range of factors known to accelerate the wound healing process. The aim of this study was to determine the impact of MAPC cells secretome on healing outcomes without the presence of MAPC cells.MethodsThe effect of MAPC-conditioned medium (MAPC-CM) on the capacity of keratinocytes, fibroblasts and endothelial cells to migrate and proliferate was determined in vitro using scratch wound closure and WST1 assay, respectively. The effect of MAPC-CM on collagen deposition and angiogenesis was also assessed using in vitro methods. Additionally, two excisional wounds were created on the dorsal surface of mice (n = 8/group) and 100 μL of 20× MAPC-CM were intradermally injected to the wound margins. Wound tissues were collected at 3, 7 and 14 days post-wounding and stained with H&E for microscopic analysis. Immunohistochemistry was performed to investigate inflammation, angiogenesis and collagen deposition in the wounds.ResultsSkin fibroblasts, keratinocytes and endothelial cells treated with MAPC-CM all showed improved rates of scratch closure and increased cellular proliferation. Moreover, fibroblasts treated with MAPC-CM deposited more collagens I and III and endothelial cells treated with MAPC-CM showed increased capillary tube formation. Murine excisional wounds intradermally injected with MAPC-CM showed a significant reduction in the wound area and an increase in the rate of reepithelialisation. The results also showed that inflammatory cell infiltration was decreased while an increase in angiogenesis, as well as collagens I and III expressions, was observed.ConclusionThese findings suggest that factors produced by MAPC cells can have an important effect on cutaneous wound healing by affecting skin cell proliferation and migration, balancing inflammation and improving the formation of extracellular matrix and angiogenesis. Development of stem cell-free therapy for the treatment of wounds may be a more clinically translatable approach for improving healing outcomes.
Highlights
Wound healing is a well-coordinated process in which various cell types receive external signals causing them to proliferate, migrate, differentiate and synthesise proteins to restore the multilayered tissue of skin [1]
Ahangar et al Stem Cell Research & Therapy (2020) 11:299 (Continued from previous page). These findings suggest that factors produced by MAPC cells can have an important effect on cutaneous wound healing by affecting skin cell proliferation and migration, balancing inflammation and improving the formation of extracellular matrix and angiogenesis
This paper aimed to investigate whether human MAPC-conditioned medium (MAPC-CM) could accelerate cutaneous wound healing in vitro and in vivo
Summary
Wound healing is a well-coordinated process in which various cell types receive external signals causing them to proliferate, migrate, differentiate and synthesise proteins to restore the multilayered tissue of skin [1]. Fibroblasts in the wound area deposit extracellular matrix (ECM) into the wound bed, which results in the formation of new granulation tissue [2]. The skin barrier is restored during the re-epithelialisation process where keratinocytes proliferate and migrate across the wound bed to form the neo-epidermis [3]. Any dysfunction in the cutaneous wound healing process such as prolonged inflammation, delayed proliferation and/or excessive collagen deposition results in the formation of chronic wounds and additional scarring in human adults [4]. Stem cell therapies have been widely investigated for their healing effects. The aim of this study was to determine the impact of MAPC cells secretome on healing outcomes without the presence of MAPC cells
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