ABSTRACT
Necrobiosis lipoidica (NL) is a rare, inflammatory granulomatous skin disorder involving collagen degeneration. In recent years, several light and laser therapies have been proposed and used in the treatment of NL with variable outcomes. The aim of the study was to investigate the efficacy and safety of lasers and light therapies for the treatment of NL. A review of PubMed was conducted to search for studies using laser and light therapies for the treatment of NL. Articles that employed a combination of treatment modalities were excluded. Twenty-four studies were reviewed. Light and laser therapies used in these studies included CO2 laser, pulsed dye laser, methyl aminolevulinate (MAL)-photodynamic therapy (PDT), aminolevulinic acid (ALA)-PDT, ultraviolet A1 (UVA1) phototherapy, and psoralen plus ultraviolet-A (PUVA). PUVA was identified as the modality with the most available evidence (7 studies), followed by MAL-PDT and ALA-PDT (5 studies each), pulsed dye laser and UVA1 (3 studies each), and lastly CO2 laser (2 studies). Most modalities demonstrated variable efficacies and side effects with the exception of PDL, which consistently showed successful outcomes. Multiple dermatologic light and laser therapies have been investigated for the treatment of NL, including PUVA, ALA-PDT, MAL-PDT, pulsed dye laser, UVA1, and CO2 laser. However, a clear consensus on the preferred treatment is yet to be addressed. Each treatment option demonstrates both advantages and disadvantages that should be discussed with patients when selecting the treatment modality.
Subject(s)
Laser Therapy , Necrobiosis Lipoidica/therapy , Phototherapy , Humans , Lasers, Dye/therapeutic use , Lasers, Gas/therapeutic use , PhotochemotherapyABSTRACT
Although chronic wounds are common and continue to be a major cause of morbidity and mortality, treatments for these conditions are lacking and often ineffective. A large body of evidence exists demonstrating the therapeutic potential of mesenchymal stem cells (MSCs) for repair and regeneration of damaged tissue, including acceleration of cutaneous wound healing. However, the exact mechanisms of wound healing mediated by MSCs are unclear. In this study, we examined the role of MSC exosomes in wound healing. We found that MSC exosomes ranged from 30 to 100-nm in diameter and internalization of MSC exosomes resulted in a dose-dependent enhancement of proliferation and migration of fibroblasts derived from normal donors and chronic wound patients. Uptake of MSC exosomes by human umbilical vein endothelial cells also resulted in dose-dependent increases of tube formation by endothelial cells. MSC exosomes were found to activate several signaling pathways important in wound healing (Akt, ERK, and STAT3) and induce the expression of a number of growth factors [hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF1), nerve growth factor (NGF), and stromal-derived growth factor-1 (SDF1)]. These findings represent a promising opportunity to gain insight into how MSCs may mediate wound healing.
Subject(s)
Exosomes/metabolism , MAP Kinase Signaling System/physiology , Mesenchymal Stem Cells/cytology , Neovascularization, Physiologic/physiology , Wound Healing/physiology , Aged , Cell Movement/physiology , Cell Proliferation/physiology , Cells, Cultured , Chemokine CXCL12/metabolism , Coculture Techniques , Diabetes Mellitus , Extracellular Signal-Regulated MAP Kinases/metabolism , Fibroblasts/metabolism , Hepatocyte Growth Factor/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Insulin-Like Growth Factor I/metabolism , Male , Nerve Growth Factor/metabolism , Proto-Oncogene Proteins c-akt/metabolism , STAT3 Transcription Factor/metabolismABSTRACT
INTRODUCTION: Recent evidence has shown that bone marrow cells play critical roles during the inflammatory, proliferative and remodeling phases of cutaneous wound healing. Among the bone marrow cells delivered to wounds are stem cells, which can differentiate into multiple tissue-forming cell lineages to effect, healing. Gaining insight into which lineages are most important in accelerating wound healing would be quite valuable in designing therapeutic approaches for difficult to heal wounds. METHODS: In this report we compared the effect of different bone marrow preparations on established in vitro wound healing assays. The preparations examined were whole bone marrow (WBM), whole bone marrow (long term initiating/hematopoietic based) cultured cells (BMC), and bone marrow derived mesenchymal stem cells (BM-MSC). We also applied these bone marrow preparations in two murine models of radiation induced delayed wound healing to determine which had a greater effect on healing. RESULTS: Angiogenesis assays demonstrated that tube formation was stimulated by both WBM and BMC, with WBM having the greatest effect. Scratch wound assays showed higher fibroblast migration at 24, 48, and 72 hours in presence of WBM as compared to BM-MSC. WBM also appeared to stimulate a greater healing response than BMC and BM-MSC in a radiation induced delayed wound healing animal model. CONCLUSIONS: These studies promise to help elucidate the role of stem cells during repair of chronic wounds and reveal which cells present in bone marrow might contribute most to the wound healing process.
Subject(s)
Bone Marrow Cells/cytology , Bone Marrow Transplantation , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Wound Healing/physiology , Animals , Bone Marrow/physiology , Cell Movement , Cell Proliferation , Cells, Cultured , Disease Models, Animal , Green Fluorescent Proteins/genetics , Human Umbilical Vein Endothelial Cells/cytology , Humans , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neovascularization, Physiologic , Radiation Injuries, Experimental/therapy , Wound Healing/radiation effectsABSTRACT
Chronic wounds continue to be a major cause of morbidity for patients and an economic burden on the health care system. Novel therapeutic approaches to improved wound healing will need, however, to address cellular changes induced by a number of systemic comorbidities seen in chronic wound patients, such as diabetes, chronic renal failure, and arterial or venous insufficiency. These effects likely include impaired inflammatory cell migration, reduced growth factor production, and poor tissue remodeling. The multifunctional properties of bone marrow-derived mesenchymal stem cells (MSCs), including their ability to differentiate into various cell types and capacity to secrete factors important in accelerating healing of cutaneous wounds, have made MSCs a promising agent for tissue repair and regeneration. In this study we have used an in vitro scratch assay procedure incorporating labeled MSCs and fibroblasts derived from normal donors and chronic wound patients in order to characterize the induction of mobilization when these cells are mixed. A modified Boyden chamber assay was also used to examine the effect of soluble factors on fibroblast migration. These studies suggest that MSCs play a role in skin wound closure by affecting dermal fibroblast migration in a dose-dependent manner. Deficiencies were noted, however, in chronic wound patient fibroblasts and MSCs as compared with those derived from normal donors. These findings provide a foundation to develop therapies targeted specifically to the use of bone marrow-derived MSCs in wound healing and may provide insight into why some wounds do not heal.