Current Stem Cell Research & Therapy - Volume 12, Issue 5, 2017

Background & Objective: The regeneration of damaged bone tissues to a pre-disease state has been a major goal for both clinicians and researchers worldwide. However, critical-sized bone defects which are unable to heal completely are a major clinical concern because effective, evidencebased regenerative therapy is still missing. Bone tissue engineering, aiming at providing novel and effective materials to promote bone regeneration, has been considered as a promising alternative to the traditional use of autografts, allografts and xenografts based on the fact that engineered bone tissue has limitless supply and has no disease transmission. Mesenchymal stem cells (MSCs) can be derived from various adult tissues such as adipose tissues, dental follicles of wisdom teeth, bone marrow, dental pulp, gingiva, etc., which do not raise any ethical concerns. Furthermore, the application of MSCs in bone tissue engineering has moved to the preclinical stage, and an ex vivo cell manufacturing procedure for obtaining high quality, bioactive MSCs from human bone marrow has been approved by the US Food and Drug Administration (FDA). Summary: In this review, we summarized the cell sources and biological characteristics of MSCs, discussed the in vivo functions of MSCs during bone regeneration, and briefly introduced the strategies for the application of MSCs in bone tissue engineering. Further research efforts are still needed to facilitate the application of MSCs in enhancing bone regeneration.

Background & Objective: Bone defects caused by bone fractures, malformations, postoperation on tumor and even periodontitis have became serious clinical problems. Although the exact origin of osteoblast precursors is still obscure, mesenchymal stem cells (MSCs) that originate from local bone marrow, periosteum, endosteum, mineralized bone or systemic circulation play key roles in osteoblastic differentiation and secretion of multiple factors during spontaneous healing of bone trauma or defect. Substantial evidences have shown that systemically infused MSCs can home and participate in bone tissue repair or regeneration. Applying pharmacological molecules to promote MSC homing or to mobilize MSCs in bone marrow niche to increase the amount of MSCs in the peripheral blood has been demonstrated to be important strategies to enhance MSC homing. However, there are some systemic conditions which influence MSC homing. Summary: In this paper, we review both systemic and local homing of MSCs during bone regeneration, and discuss strategies for enhancing the recruitment of MSCs to the injured bone tissues. Systemic influences of MSC homing are also discussed.

Background: Various clinical studies have revealed that cardiovascular diseases (CVD) are associated with bone loss diseases such as osteoporosis and periodontitis, especially in older population. As one of the best-established risk factors of CVD, hyperlipidemia is also reported to interfere with the metabolism, function and regeneration of mineralized tissues. Derived from postnatal tissue reservoirs, mesenchymal stem cells (MSCs) are considered promising cell sources for mesenchymal and non-mesenchymal tissue regeneration based on their capacities for self-renewal and multi-lineage differentiation as well as potent immunosuppressive effects, secretion of cytokines and regulation of vascularization. MSCs could home to the injury sites from peripheral circulation, proliferate and differentiate into bone-forming cells, therefore significantly enhancing bone regeneration. However, elevated blood lipid levels affect the physiological behaviors of MSCs, as well as the performance of transplanted MSCs. Objective: This review aims to summarize the effects of hyperlipidemia and CVD on the proliferation, osteogenic differentiation and homing of MSCs. The principal observations of the underlying cellular and molecular mechanisms as well as the effects of lipid-lowering therapy on MSCs are also discussed.

Background: Diabetes mellitus (DM) is a widespread chronic metabolic disease which has high mortality due to its complications. In addition to traditional medication, stem cell transplantation therapeutics has become a brand-new and prospective remedy for DM. With strong self-renewal and multi-potential ability, mesenchymal stem cells (MSCs) are considered as ideal cell sources of cell therapy for DM and many other diseases. However, not only do endogenous MSCs fail to replace the impaired islet cells, but also transplanted MSCs fail to cure many patients complicated with DM. Besides, quite a few DM patients suffer from high risk of fracture and low efficiency of bone regeneration, which are often associated with the osteoblastic differentiation of MSCs. Recently, a number of researches have investigated that the changes in micro-environment by DM can affect biological characteristics of MSCs through many factors. Summary: In this review, we summarize the developments in the influence of DM on proliferation and osteoblastic differentiation of MSCs, and moreover, osteoporosis, obesity and metabolism syndrome, as they are closely related to DM.

Background: Mesenchymal stem cells (MSCs) have been widely researched for the function of wound repair and bone regeneration. Numerous evidence have proved that MSCs can differentiate towards osteoblasts, and enhance bone formation, and then directly promote the process of bone regeneration. Objective: The researchers’ interest in MSCs focuses on the potential of differentiating towards osteoblasts. They suggest that these applications can be significantly influenced by different kinds of inflammatory cytokines. In particular, in the process of bone regeneration, MSCs and inflammatory cytokines interact with each other, and promote the process of bone healing. In this review, we attempt to summarize several inflammatory cytokines that may have influence on the osteogenic differentiation of MSCs, including interleukin 1 (IL-1), IL-6, IL-10, IL-17, tumor necrosis factor-α (TNF-α ), and interferon-γ (INF-γ ), bone morphogenetic proteins(BMPs). Finally, some perspective of the behavior of MSCs in response to inflammatory cytokines are discussed.

Background: Mesenchymal stem cells not only possess reparative properties, but also have immunomodulatory effect. Owing to the properties, they have been proposed to be hopeful candidates for cell therapy in the process of organ transplantation. In the preclinical researches, it shows that MSCs is capable of prolonging graft survival and inducing tolerance in some cases. Various mechanisms of immune tolerance were reported before, such as tolerogenic dendritic cells, induction of apoptosis, regulatory T cells, mixed chimerism, soluble factors and anergy. Furthermore, the induction of immune tolerance may be influenced by the dose, route and optimal timing of MSCs administration. Allograft of skin can provisionally restore the function of skin barrier and offer a good environment to expand micro-skin auto-graft; however, at the same time, it can cause strong immune rejection, which leads to the failure of skin graft. Objective: The review aims at analyzing the mechanisms of immunosuppression mediated by MSCs, and the induction of tolerance of skin graft by MSCs. Conclusion: Mesenchymal stem cells are hopeful candidates for cell therapy in the process of organ transplantation, and can induce immune tolerance of skin graft to some extent.

Background: Recently, some studies identified the Basic-Helix-Loop-Helix (bHLH) transcription factor as a significant regulator for the evolution of neoplasms. The binding between bHLH proteins and DNA is restricted by heterodimerization with Inhibitors of DNA binding (ID). IDs prevent cellular differentiation, promote growth and sustain tumor development. The wide presence of stem cells in cancers suggests that genes ID are essential to cancer stem cells (CSC) progress. The enzyme Ubiquitin-specific protease 1 (USP1) is reported to deubiquitinate and stabilize IDs. Considering the action of the proteins ID, USP1 contributes to prevent differentiation mediated by bHLH and, consequently, keep CSC original characteristics. USP1 has its activity potentiated when bound to protein WD repeat-containing protein (WDR48). Objective: To identify the influence of the complex USP1/WDR48 during the CSC tumorigenesis process, and whether this complex is a possible therapeutic target. Methods: A literature search regarding the role of the complex USP1/WDR48 in inhibiting differentiation and increasing proliferation of CSC was performed, and possible selective molecule inhibitors of these deubiquitinase proteins were investigated. Results: There is evidence that USP1/WDR48 complex promotes stem cell conservation and regulation of DNA damage repair. For this reason, inhibitors as Pimozide, GW7647, C527, SJB2-043, ML323 have been studied to inhibit USPs in cases of treatment intervention. Conclusion: It is consolidated in the literature the role of USP1/WDR48 during tumorigenesis. However, these studies are not enough to completely clarify the process; but certainly, the researchers are converging towards a promising direction to provide a new treatment option for cancer.

Background: Kidney diseases are a public health problem worldwide. Available therapies include function replacement by dialysis or transplant, which are associated with a high morbidity and mortality. Likewise, none of these treatments compensate all kidney functions. There is a great concern in developing more effective therapies with the ability to replace the wide range of renal functions, so that, new studies on developing therapeutic strategies have focused on regenerative medicine. Objective: The aim of this paper is to review the new advances in regenerative medicine for renal failure treatment. Results: Regenerative medicine comprises two therapeutic strategies: cell therapy and tissue engineering. Cell therapy techniques depend on cell and tissue cultures, with the aim to replace morphological structures, tissues, and functions. The main strategic strength of cell therapy in renal failure is the incorporation of additional cells in a damaged kidney, for which purpose different kind of Stem Cells (SCs) have been used such as Embryonic SCs, induced Pluripotent SCs, Multipotent SCs, Renal SCs, or drugs that increase survival and mobilization of SCs. Tissue engineering complements cell therapy combining techniques of biological sciences and engineering to create structures and devices as scaffolds, matrices or 3D biocompatible materials. Conclusion: Even though there is a significant advance in regenerative medicine strategies, we are far from using any of its techniques on health institutions, due to it is necessary to evaluate side effects, biodistribution, dosage, type of administration, vehicle of cell therapy, as well as the evaluation of response time and long-term studies, among other studies.

Background: Bone marrow stem cells (BMSCs) and adipose-derived stem cells (ADSCs) are two types of stem cells that commonly used in exogenous tissue engineering as well as endogenous tissue repair, however which type of cell is superior remains unknown. Objective: This study was conducted to compare differentiation potential of BMSCs and ADSCs from Sprague-Dawley rats towards annulus fibrosus (AF)-like cells. Method: Stem cells and AF cells were cocultured with direct cell-to-cell contact in coculture plates with 0.4μm pore size up till 21 days. AF markers expression at the histological level and molecular level were evaluated by histological analysis and dimethplmethplene blue (DMMB) assay as well as quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Results: qRT-PCR) results showed up regulation in AF marker gene expressions of both two MSCs after coculture. BMSCs demonstrated a statistically increased expression of collagen II and aggrecan from 7 days of coculture. However, these gene expressions in ADSCs showed a statistically increase at day 14 and day 21. And there was a statistically increase of Collagen I expression in BMSCs at 14 days and 21 days. But only after 21 days of coculture, ADSCs showed a statistically increase in collagen I expression. Moreover, histological analysis and dimethplmethplene blue (DMMB) assay mirrored the results of qRT-PCR. Morphologically, BMSCs became enlarged and triangular, while ADSCs were enlarged and rounded after coculture. Conclusion: These findings suggested that BMSCs might be superior as a cell source for annulus fibrosus repair compared to ADSCs.