Mesenchymal Stem Cells-Derived Exosomes for Wound Regeneration.

Wound healing is a complex process with the considerable burden on healthcare system. There are several cellular therapy methods that have been introduced to treat different types of wounds. Despite the advantages of cellular therapy, it is needed to overcome different limitations of this method such as; tumorigenicity and immune rejection. Accordingly, scientists have suggested cell-based vesicles and exosomes. Exosomes can promote proliferation, migration, and angiogenesis process in the wound environment. They have also some advantages such as the potential for drug and gene delivery, easy to storage, and stability in the body. These advantages make them as a novel approach in regenerative medicine without the limitations of cellular therapy. In this review, the authors emphasize on biological properties of MSC-exosomes and their therapeutic effects as a new strategy for wound regeneration.

Stem Cell and Obesity: Current State and Future Perspective.

Obesity as a worldwide growing challenge is determined by abnormal fat deposition, which may damage general health. Weight loss and control of related risk factors like type2 diabetes, dyslipidemia, hypertension, cardiovascular diseases, and metabolic syndrome is an important concern in obesity management. Different therapeutic approaches such as lifestyle change, medications, and surgery are introduced for obesity treatment. Despite of gaining partially desirable results, the problem is remained unsolved. Therefore, finding a new approach that can overcome previous limitations is very attractive for both researchers and clinicians. Cell-based therapy using adipose-derived stromal cells seems to be a promising strategy to control obesity and related syndromes. To attain this aim, understanding of different type of adipose tissues, main signaling pathways, and different factors involved in development of adipocyte is essential. Recently, several cell-based methods like stem cell administration, brown adipose tissue transplantation, cell lysates and exosomes have been examined on obese mouse models to manage obesity and related disorders. Successful outcome of such preclinical studies can encourage the cell-based clinical trials in the near future.

Tissue Engineered Skin Substitutes.

The fundamental skin role is to supply a supportive barrier to protect body against harmful agents and injuries. Three layers of skin including epidermis, dermis and hypodermis form a sophisticated tissue composed of extracellular matrix (ECM) mainly made of collagens and glycosaminoglycans (GAGs) as a scaffold, different cell types such as keratinocytes, fibroblasts and functional cells embedded in the ECM. When the skin is injured, depends on its severity, the majority of mentioned components are recruited to wound regeneration. Additionally, different growth factors like fibroblast growth factor (FGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) are needed to orchestrated wound healing process. In case of large surface area wounds, natural wound repair seems inefficient. Inspired by nature, scientists in tissue engineering field attempt to engineered constructs mimicking natural healing process to promote skin restoration in untreatable injuries. There are three main types of commercially available engineered skin substitutes including epidermal, dermal, and dermoepidermal. Each of them could be composed of scaffold, desired cell types or growth factors. These substitutes could have autologous, allogeneic, or xenogeneic origin. Moreover, they may be cellular or acellular. They are used to accelerate wound healing and recover normal skin functions with pain relief. Although there are a wide variety of commercially available skin substitutes, almost none of them considered as an ideal equivalents required for proper wound healing.

Adipose Tissue-Derived Stromal Cells for Wound Healing.

Skin as the outer layer covers the body. Wounds can affect this vital organ negatively and disrupt its functions. Wound healing as a biological process is initiated immediately after an injury. This process consists of three stages: inflammation, proliferation, remodeling. Generally, these three stages occur continuously and timely. However, some factors such as infection, obesity and diabetes mellitus can interfere with these stages and impede the normal healing process which results in chronic wounds. Financial burden on both patients and health care systems, negative biologic effect on the patient's general health status and reduction in quality of life are a number of issues which make chronic wounds as a considerable challenge. During recent years, along with advances in the biomedical sciences, various surgical and non-surgical therapeutic methods have been suggested. All of these suggested treatments have their own advantages and disadvantages. Recently, cell-based therapies and regenerative medicine represent promising approaches to wound healing. Accordingly, several types of mesenchymal stem cells have been used in both preclinical and clinical settings for the treatment of wounds. Adipose-derived stromal cells are a cost-effective source of mesenchymal stem cells in wound management which can be easily harvest from adipose tissues through the less invasive processes with high yield rates. In addition, their ability to secrete multiple cytokines and growth factors, and differentiation into skin cells make them an ideal cell type to use in wound treatment. This is a concise overview on the application of adipose-derived stromal cells in wound healing and their role in the treatment of chronic wounds.

Personalized Regenerative Medicine.

Personalized medicine as a novel field of medicine refers to the prescription of specific therapeutics procedure for an individual. This approach has established based on pharmacogenetic and pharmacogenomic information and data. The terms precision and personalized medicines are sometimes applied interchangeably. However, there has been a shift from "personalized medicine" towards "precision medicine". Although personalized medicine emerged from pharmacogenetics, nowadays it covers many fields of healthcare. Accordingly, regenerative medicine and cellular therapy as the new fields of medicine use cell-based products in order to develop personalized treatments. Different sources of stem cells including mesenchymal stem cells, embryonic stem cells and induced pluripotent stem cells (iPSCs) have been considered in targeted therapies which could give many advantages. iPSCs as the novel and individual pluripotent stem cells have been introduced as the appropriate candidates for personalized cell therapies. Cellular therapies can provide a personalized approach. Because of person-to-person and population differences in the result of stem cell therapy, individualized cellular therapy must be adjusted according to the patient specific profile, in order to achieve best therapeutic results and outcomes. Several factors should be considered to achieve personalized stem cells therapy such as, recipient factors, donor factors, and the overall body environment in which the stem cells could be active and functional. In addition to these factors, the source of stem cells must be carefully chosen based on functional and physical criteria that lead to optimal outcomes.

Differential Incorporation of ß-actin as A Component of RNA Polymerase II into Regulatory Regions of Stemness/Differentiation Genes in Retinoic Acid-Induced Differentiated Human Embryonic Carcinoma Cells.

OBJECTIVE: Nuclear actin is involved in transcription regulation by recruitment of histone modifiers and chromatin remodelers to the regulatory regions of active genes. In recent years, further attention has been focused on the role of actin as a nuclear protein in transcriptional processes. In the current study, the epigenetic role of nuclear actin on transcription regulation of two stemness (OCT4 and NANOG) and two differentiation) NESTIN and PAX6) marker genes was evaluated in a human embryonal carcinoma cell line (NT2) before and after differentiation induction. MATERIALS AND METHODS: In this experimental study, differentiation of embryonal cells was induced by retinoic acid (RA), and quantitative real-time polymerase chain reaction (PCR) was used to evaluate differential expression of marker genes before and 3 days after RA- induced differentiation. Chromatin immunoprecipitation (ChIP) coupled with real-time PCR was then undertaken to monitor the incorporation of ß-actin, as a functional component of RNA polymerase II, in the regulatory regions of marker genes. RESULTS: Data showed significant change in nuclear actin incorporation into the promoter regions of NESTIN and PAX6 after RA-induction. CONCLUSION: We emphasize the dynamic functional role of nuclear actin in differentiation of embryonal cells and its role as a subunit of RNA polymerase II.

A simple and cost-effective method for isolation and expansion of human fetal pancreas derived mesenchymal stem cells.

BACKGROUND: Previous studies have suggested mesenchymal stem cells (MSCs) as a suitable source for cell replacement therapy in diabetes. MSCs have successfully isolated from different adult and fetal tissues, including the pancreas. In vitro studies have shown that human fetal pancreatic stem cells could be extensively expanded and differentiated into islet-like structures. Here, we introduce a simple and cost-effective method for the generation of MSCs from the human fetal pancreas (FPMSCs). METHODS: To isolate FPMSCs, pancreata from four aborted fetuses (second trimester) were processed with short collagenase digestion. The resulting tissue fragments were transferred to a basic media (DMEM+15%FBS) without adding any growth factor. RESULTS: After 10 to14 days, fibroblast-like cells were harvested and passaged six times for further evaluations. Flow cytometry analysis and three-lineage differentiation capacity have demonstrated that these cells have MSC-like properties. We also continuously passaged samples of FPMSCs and found no evidence for chromosomal instability and morphological changes until 10th subculture. Moreover, our cell culture protocol can be easily modified and translated into a GMP-compliant one. CONCLUSION: The results of current study demonstrated that our simple and inexpensive method could yield a pure population of FPMSCs that might be suitable for transplantation.

Human fetal skin fibroblasts: Extremely potent and allogenic candidates for treatment of diabetic wounds.

The number of patients with diabetes has been expected around 300 million by 2025 and 366 million by 2030 by WHO. On the other hand, diabetic wounds as one of the common complications of diabetes represent major health challenges. Recently, wound care biological products have been proposed for treatment of chronic wounds such as the diabetic wound. Accordingly, tissue-engineered skin substitutes have demonstrated promising effects. Some of these products have used adult skin and neonatal foreskin fibroblasts to produce a tissue-engineered skin substitute. Although adult skin and neonatal foreskin fibroblasts have demonstrated promising effects, but fetal skin fibroblasts and keratinocytes have depicted some unique and considerable properties over adult and neonatal skin cells for instance, skin regeneration with no inflammation and scar formation, low immunogenicity, more VEGF-A secretion than their adult counterparts, immunomodulatory effect by the expression of Indoleamine 2,3 dioxygenase, more resistance to oxidative and physical stresses, etc. On the other hand fetal dermal cells with intrinsic IDO-dependent immunosuppressive activity have introduced them as an allogeneic alternative for treatment of chronic wounds. Therefore, based on the mentioned advantages they are ideal skin substitutes. Accordingly, we suggest that using these cells alone or in combination with biocompatible scaffolds for treatment of different types of ulcers such as diabetic wounds.