Efficacious and Clinically Relevant Conditioned Medium of Human Adipose-derived Stem Cells for Therapeutic Angiogenesis

Background. Stem cell-derived conditioned medium has a promising prospect to be produced as pharmaceuticals for regenerative medicine. Objective. To investigate various methods to obtain stem cell-derived conditioned medium (CM) to get an insight into their prospect of application in various diseases. Methods. Systematic review using keywords “stem cell” and “conditioned medium” or “secretome” and “therapy.” Data concerning treated conditions/diseases, type of cell that was cultured, medium and supplements to culture the cells, culture condition, CM processing, growth factors and other secretions that were analyzed, method of application, and outcome were noted, grouped, tabulated, and analyzed. Results. Most of CM using studies showed good results. However, the various CM, even when they were derived from the same kind of cells, were produced by different condition, that is, from different passage, culture medium, and culture condition. The growth factor yields of the various types of cells were available in some studies, and the cell number that was needed to produce CM for one application could be computed. Conclusion. Various stem cell-derived conditioned media were tested on various diseases and mostly showed good results. However, standardized methods of production and validations of their use need to be conducted.

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“…Moreover, different culture condition and medium may yield different level of growth factor secretions [6]. …”

Section: Resultsmentioning

confidence: 99%

Prospect of Stem Cell Conditioned Medium in Regenerative Medicine

Pawitan

2014

BioMed Research International

362

320

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“…Among various types of stem cells, mesenchymal stem cells (MSCs) have been demonstrated to have beneficial functional effects in cardiomyogenesis [9], tendon repair [10], bone regeneration [11] and dermal wound healing [12]. In addition, MSCs have been reported to contribute to wound healing by improving neovascularization and reducing scar formation, by encouraging direct differentiation, and by potent paracrine signaling that supports angiogenesis [13–15]. However, current sources of MSCs require invasive procurement procedures that provide a relatively low amount of progenitor cells.…”

Section: Introductionmentioning

confidence: 99%

Accelerated wound healing in a diabetic rat model using decellularized dermal matrix and human umbilical cord perivascular cells

et al. 2016

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There is an unmet clinical need for novel wound healing strategies to treat full thickness skin defects, especially in diabetic patients. We hypothesized that a scaffold could perform dual roles of a biomechanical support and a favorable biochemical environment for stem cells. Human umbilical cord perivascular cells (HUCPVCs) have been recently reported as a type of mesenchymal stem cell that can accelerate early wound healing in skin defects. However, there are only a limited number of studies that have incorporated these cells into natural scaffolds for dermal tissue engineering. The aim of the present study was to promote angiogenesis and accelerate wound healing by using HUCPVCs and decellularized dermal matrix (DDM) in a rat model of diabetic wounds. The DDM scaffolds were prepared from harvested human skin samples and histological, ultrastructural, molecular and mechanical assessments were carried out. In comparison with the control (without any treatment) and DDM alone group, full thickness excisional wounds treated with HUCPVCs-loaded DDM scaffolds demonstrated an accelerated wound closure rate, faster re-epithelization, more granulation tissue formation and decreased collagen deposition. Furthermore, immunofluorescence analysis showed that the VEGFR-2 expression and vascular density in the HUCPVCs-loaded DDM scaffold treated group were also significantly higher than the other groups at 7 days post implantation. Since the rates of angiogenesis, re-epithelization and formation of granulation tissue are directly correlated with full thickness wound healing in patients, the proposed HUCPVCs-loaded DDM scaffolds may fulfil a role neglected by current treatment strategies. This pre-clinical proof-of-concept study warrants further clinical evaluation. Statement of Significance The aim of the present study was to design a novel tissue-engineered system to promote angiogenesis, re-epithelization and granulation of skin tissue using human umbilical cord perivascular stem cells and decellularized dermal matrix natural scaffolds in rat diabetic wound models. The authors of this research article have been working on stem cells and tissue engineering scaffolds for years. According to our knowledge, there is a lack of an efficient system for the treatment of skin defects using tissue engineering strategy. Since the rates of angiogenesis, re-epithelization and granulation tissue are directly correlated with full thickness wound healing, the proposed HUCPVCs-loaded DDM scaffolds perfectly fills the niche neglected by current treatment strategies. This pre-clinical study demonstrates the proof-of-concept that necessitates clinical evaluations.

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“…In this view, conditioned medium from human ASCs is effective enough to improve blood vessel density, limb salvage, and blood perfusion in mice with CLI. [7] This paracrine mechanism includes the release of vascular growth factors, anti-apoptotic/pro-survival factors, vasoactive molecules, interleukins (IL), and chemokines with potent effects on vascular growth and remodeling. [3] As for bone-marrowderived cells, one can also speculate that these molecules could be clustered and cargo to the vascular compartment within extracellular membrane vesicles including microparticles and exosomes.…”

Section: Stem Cell Therapies For Peripheral Arterial Diseasesmentioning

confidence: 99%