Showing papers on "Stem-cell therapy published in 2017"
TL;DR: 3D printed pre-vascularized stem cell patch can enhance the therapeutic efficacy for cardiac repair through promotion of rapid vascularization after patch transplantation and provides cardiac niche-like microenvironment, resulting in beneficial effects on cardiac repair.
462 citations
TL;DR: It is proposed that cell surface marker profiles, bone‐forming capacities in ectopic and orthotopic models, and other functionalities of MSCs should be characterized prior to use in clinical applications as part of comprehensive and uniform guidelines and release criteria for their clinical‐grade production to achieve predictably favorable treatment outcomes for stem cell therapy.
Abstract: Mesenchymal stem cells (MSC) hold great potential for regenerative medicine because of their ability for self-renewal and differentiation into tissue-specific cells such as osteoblasts, chondrocytes, and adipocytes. MSCs orchestrate tissue development, maintenance and repair, and are useful for musculoskeletal regenerative therapies to treat age-related orthopedic degenerative diseases and other clinical conditions. Importantly, MSCs produce secretory factors that play critical roles in tissue repair that support both engraftment and trophic functions (autocrine and paracrine). The development of uniform protocols for both preparation and characterization of MSCs, including standardized functional assays for evaluation of their biological potential, are critical factors contributing to their clinical utility. Quality control and release criteria for MSCs should include cell surface markers, differentiation potential, and other essential cell parameters. For example, cell surface marker profiles (surfactome), bone-forming capacities in ectopic and orthotopic models, as well as cell size and granularity, telomere length, senescence status, trophic factor secretion (secretome), and immunomodulation, should be thoroughly assessed to predict MSC utility for regenerative medicine. We propose that these and other functionalities of MSCs should be characterized prior to use in clinical applications as part of comprehensive and uniform guidelines and release criteria for their clinical-grade production to achieve predictably favorable treatment outcomes for stem cell therapy. Stem Cells Translational Medicine 2017;6:2173-2185.
455 citations
TL;DR: This review will focus on recent advances in stem cell therapies utilizing animal models of AD, as well as detailing the human clinical trials ofstem cell therapies for AD that are currently undergoing development.
Abstract: Alzheimer’s disease (AD) represents arguably the most significant social, economic, and medical crisis of our time. Characterized by progressive neurodegenerative pathology, AD is first and foremost a condition of neuronal and synaptic loss. Repopulation and regeneration of depleted neuronal circuitry by exogenous stem cells is therefore a rational therapeutic strategy. This review will focus on recent advances in stem cell therapies utilizing animal models of AD, as well as detailing the human clinical trials of stem cell therapies for AD that are currently undergoing development.
210 citations
TL;DR: In a mouse model of myocardial infarction, injection of CMMPs leads to the preservation of viable myocardium and augmentation of cardiac functions similar to cardiac stem cell therapy, andCMMPs act as 'synthetic stem cells’ which mimic the paracrine and biointerfacing activities of natural stem cells in therapeutic cardiac regeneration.
Abstract: Stem cell therapy represents a promising strategy in regenerative medicine. However, cells need to be carefully preserved and processed before usage. In addition, cell transplantation carries immunogenicity and/or tumourigenicity risks. Mounting lines of evidence indicate that stem cells exert their beneficial effects mainly through secretion (of regenerative factors) and membrane-based cell-cell interaction with the injured cells. Here, we fabricate a synthetic cell-mimicking microparticle (CMMP) that recapitulates stem cell functions in tissue repair. CMMPs carry similar secreted proteins and membranes as genuine cardiac stem cells do. In a mouse model of myocardial infarction, injection of CMMPs leads to the preservation of viable myocardium and augmentation of cardiac functions similar to cardiac stem cell therapy. CMMPs (derived from human cells) do not stimulate T-cell infiltration in immuno-competent mice. In conclusion, CMMPs act as 'synthetic stem cells' which mimic the paracrine and biointerfacing activities of natural stem cells in therapeutic cardiac regeneration.
194 citations
TL;DR: It is highlighted that MSCs, with a proven track record of safety and efficacy as a transplantable cell for hematologic diseases, stand as an attractive cell type that confers superior anti‐inflammatory effects in stroke both in vitro and in vivo.
190 citations
TL;DR: A novel mechanism by which cell-free CD34Exo mediates ischemic tissue repair via beneficial angiogenesis is demonstrated and may explain the angiogenic and therapeutic benefits associated with CD34+ stem cell therapy.
Abstract: Rationale: Paracrine secretions seem to mediate therapeutic effects of human CD34 + stem cells locally transplanted in patients with myocardial and critical limb ischemia and in animal models. Earlier, we had discovered that paracrine secretion from human CD34 + cells contains proangiogenic, membrane-bound nanovesicles called exosomes (CD34Exo). Objective: Here, we investigated the mechanisms of CD34Exo-mediated ischemic tissue repair and therapeutic angiogenesis by studying their miRNA content and uptake. Methods and Results: When injected into mouse ischemic hindlimb tissue, CD34Exo, but not the CD34Exo-depleted conditioned media, mimicked the beneficial activity of their parent cells by improving ischemic limb perfusion, capillary density, motor function, and their amputation. CD34Exo were found to be enriched with proangiogenic miRNAs such as miR-126-3p. Knocking down miR-126-3p from CD34Exo abolished their angiogenic activity and beneficial function both in vitro and in vivo. Interestingly, injection of CD34Exo increased miR-126-3p levels in mouse ischemic limb but did not affect the endogenous synthesis of miR-126-3p, suggesting a direct transfer of stable and functional exosomal miR-126-3p. miR-126-3p enhanced angiogenesis by suppressing the expression of its known target, SPRED1 , simultaneously modulating the expression of genes involved in angiogenic pathways such as VEGF (vascular endothelial growth factor), ANG1 (angiopoietin 1), ANG2 (angiopoietin 2), MMP9 (matrix metallopeptidase 9), TSP1 (thrombospondin 1), etc. Interestingly, CD34Exo, when treated to ischemic hindlimbs, were most efficiently internalized by endothelial cells relative to smooth muscle cells and fibroblasts, demonstrating a direct role of stem cell–derived exosomes on mouse endothelium at the cellular level. Conclusions: Collectively, our results have demonstrated a novel mechanism by which cell-free CD34Exo mediates ischemic tissue repair via beneficial angiogenesis. Exosome-shuttled proangiogenic miRNAs may signify amplification of stem cell function and may explain the angiogenic and therapeutic benefits associated with CD34 + stem cell therapy.
183 citations
TL;DR: This study indicates that the exosomes act as an important vehicle in information exchange between BM-MSCs and NPCs and would be an appropriate option in a cell-free therapy strategy for intervertebral disc degeneration.
Abstract: The stem cell-based therapies for intervertebral disc degeneration have been widely studied. However, the mechanisms of mesenchymal stem cells interacting with intervertebral disc cells, such as nucleus pulposus cells (NPCs), remain unknown. Exosomes as a vital paracrine mechanism in cell–cell communication have been highly focused on. The purpose of this study was to detect the role of exosomes derived from bone marrow mesenchymal stem cells (BM-MSCs) and NPCs in their interaction with corresponding cells. The exosomes secreted by BM-MSCs and NPCs were purified by differential centrifugation and identified by transmission electron microscope and immunoblot analysis of exosomal marker proteins. Fluorescence confocal microscopy was used to examine the uptake of exosomes by recipient cells. The effects of NPC exosomes on the migration and differentiation of BM-MSCs were determined by transwell migration assays and quantitative RT-PCR analysis of NPC phenotypic genes. Western blot analysis was performed to examine proteins such as aggrecan, sox-9, collagen II and hif-1α in the induced BM-MSCs. Proliferation and the gene expression profile of NPCs induced by BM-MSC exosomes were measured by Cell Counting Kit-8 and qRT-PCR analysis, respectively. Both the NPCs and BM-MSCs secreted exosomes, and these exosomes underwent uptake by the corresponding cells. NPC-derived exosomes promoted BM-MSC migration and induced BM-MSC differentiation to a nucleus pulposus-like phenotype. BM-MSC-derived exosomes promoted NPC proliferation and healthier extracellular matrix production in the degenerate NPCs. Our study indicates that the exosomes act as an important vehicle in information exchange between BM-MSCs and NPCs. Given a variety of functions and multiple advantages, exosomes alone or loaded with specific genes and drugs would be an appropriate option in a cell-free therapy strategy for intervertebral disc degeneration.
152 citations
TL;DR: The fabricated synMSC therapeutic particle demonstrated its regenerative potential in mice with acute myocardial infarction and may provide novel insight into tissue engineering for treating multiple diseases.
Abstract: Rationale: Stem cell therapy faces several challenges. It is difficult to grow, preserve, and transport stem cells before they are administered to the patient. Synthetic analogs for stem cells represent a new approach to overcome these hurdles and hold the potential to revolutionize regenerative medicine. Objective: We aim to fabricate synthetic analogs of stem cells and test their therapeutic potential for treatment of acute myocardial infarction in mice. Methods and Results: We packaged secreted factors from human bone marrow–derived mesenchymal stem cells (MSC) into poly(lactic-co-glycolic acid) microparticles and then coated them with MSC membranes. We named these therapeutic particles synthetic MSC (or synMSC). synMSC exhibited a factor release profile and surface antigens similar to those of genuine MSC. synMSC promoted cardiomyocyte functions and displayed cryopreservation and lyophilization stability in vitro and in vivo. In a mouse model of acute myocardial infarction, direct injection of synMSC promoted angiogenesis and mitigated left ventricle remodeling. Conclusions: We successfully fabricated a synMSC therapeutic particle and demonstrated its regenerative potential in mice with acute myocardial infarction. The synMSC strategy may provide novel insight into tissue engineering for treating multiple diseases.
131 citations
TL;DR: The current advances in the exosomes from iPSC derivatives are focused on and their therapeutic potential in the treatment of CVD is discussed.
Abstract: Cardiovascular disease (CVD) is the leading cause of death in modern society. The adult heart innately lacks the capacity to repair and regenerate the damaged myocardium from ischemic injury. Limited understanding of cardiac tissue repair process hampers the development of effective therapeutic solutions to treat CVD such as ischemic cardiomyopathy. In recent years, rapid emergence of induced pluripotent stem cells (iPSC) and iPSC-derived cardiomyocytes presents a valuable opportunity to replenish the functional cells to the heart. The therapeutic effects of iPSC-derived cells have been investigated in many preclinical studies. However, the underlying mechanisms of iPSC-derived cell therapy are still unclear, and limited engraftment of iPSC-derived cardiomyocytes is well known. One facet of their mechanism is the paracrine effect of the transplanted cells. Microvesicles such as exosomes secreted from the iPSC-derived cardiomyocytes exert protective effects by transferring the endogenous molecules to salvage the injured neighboring cells by regulating apoptosis, inflammation, fibrosis, and angiogenesis. In this review, we will focus on the current advances in the exosomes from iPSC derivatives and discuss their therapeutic potential in the treatment of CVD.
130 citations
TL;DR: The bioengineering technologies developed for tooth regeneration will make substantial contributions to understand the developmental process and will encourage future organ replacement by regenerative therapies in a wide variety of organs such as the liver, kidney, and heart.
Abstract: Stem cell biology has become an important field in regenerative medicine and tissue engineering therapy since the discovery and characterization of mesenchymal stem cells Stem cell populations have also been isolated from human dental tissues, including dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla, dental follicle progenitor cells, and periodontal ligament stem cells Dental stem cells are relatively easily obtainable and exhibit high plasticity and multipotential capabilities The dental stem cells represent a gold standard for neural-crest-derived bone reconstruction in humans and can be used for the repair of body defects in low-risk autologous therapeutic strategies The bioengineering technologies developed for tooth regeneration will make substantial contributions to understand the developmental process and will encourage future organ replacement by regenerative therapies in a wide variety of organs such as the liver, kidney, and heart The concept of developing tooth banking and preservation of dental stem cells is promising Further research in the area has the potential to herald a new dawn in effective treatment of notoriously difficult diseases which could prove highly beneficial to mankind in the long run
128 citations
TL;DR: The results support further clinical development of the BCL11A erythroid-specific enhancer editing in BM-CD34+ HSPCs as an autologous stem cell therapy in SCD patients.
Abstract: To develop an effective and sustainable cell therapy for sickle cell disease (SCD), we investigated the feasibility of targeted disruption of the BCL11A gene, either within exon 2 or at the GATAA motif in the intronic erythroid-specific enhancer, using zinc finger nucleases in human bone marrow (BM) CD34+ hematopoietic stem and progenitor cells (HSPCs). Both targeting strategies upregulated fetal globin expression in erythroid cells to levels predicted to inhibit hemoglobin S polymerization. However, complete inactivation of BCL11A resulting from bi-allelic frameshift mutations in BCL11A exon 2 adversely affected erythroid enucleation. In contrast, bi-allelic disruption of the GATAA motif in the erythroid enhancer of BCL11A did not negatively impact enucleation. Furthermore, BCL11A exon 2-edited BM-CD34+ cells demonstrated a significantly reduced engraftment potential in immunodeficient mice. Such an adverse effect on HSPC function was not observed upon BCL11A erythroid-enhancer GATAA motif editing, because enhancer-edited CD34+ cells achieved robust long-term engraftment and gave rise to erythroid cells with elevated levels of fetal globin expression when chimeric BM was cultured ex vivo. Altogether, our results support further clinical development of the BCL11A erythroid-specific enhancer editing in BM-CD34+ HSPCs as an autologous stem cell therapy in SCD patients.
TL;DR: Stem cell-derived exosomes emerge as a critical player in paracrine mechanism of stem cell-based therapy and it is promising to exploit exosome-based cell-free therapy for ischemic heart diseases in the future.
Abstract: Introduction Ischemic heart diseases, especially the myocardial infarction, is a major hazard problem to human health. Despite substantial advances in control of risk factors and therapies with drugs and interventions including bypass surgery and stent placement, the ischemic heart diseases usually result in heart failure (HF), which could aggravate social burden and increase the mortality rate. The current therapeutic methods to treat HF stay at delaying the disease progression without repair and regeneration of the damaged myocardium. While heart transplantation is the only effective therapy for end-stage patients, limited supply of donor heart makes it impossible to meet the substantial demand from patients with HF. Stem cell-based transplantation is one of the most promising treatment for the damaged myocardial tissue. Sources of data Key recent published literatures and ClinicalTrials.gov. Areas of agreement Stem cell-based therapy is a promising strategy for the damaged myocardial tissue. Different kinds of stem cells have their advantages for treatment of Ischemic heart diseases. Areas of controversy The efficacy and potency of cell therapies vary significantly from trial to trial; some clinical trials did not show benefit. Diverged effects of cell therapy could be affected by cell types, sources, delivery methods, dose and their mechanisms by which delivered cells exert their effects. Growing points Understanding the origin of the regenerated cardiomyocytes, exploring the therapeutic effects of stem cell-derived exosomes and using the cell reprogram technology to improve the efficacy of cell therapy for cardiovascular diseases. Areas timely for developing research Recently, stem cell-derived exosomes emerge as a critical player in paracrine mechanism of stem cell-based therapy. It is promising to exploit exosomes-based cell-free therapy for ischemic heart diseases in the future.
TL;DR: The importance of understanding the mechanisms of cardiac repair and the lessons learned from first-generation trials, in order to improve cell-based therapies and to potentially finally implement cell-free therapies is emphasized.
Abstract: Acute myocardial infarction and chronic heart failure rank among the major causes of morbidity and mortality worldwide. Except for heart transplantation, current therapy options only treat the symptoms but do not cure the disease. Stem cell-based therapies represent a possible paradigm shift for cardiac repair. However, most of the first-generation approaches displayed heterogeneous clinical outcomes regarding efficacy. Stemming from the desire to closely match the target organ, second-generation cell types were introduced and rapidly moved from bench to bedside. Unfortunately, debates remain around the benefit of stem cell therapy, optimal trial design parameters, and the ideal cell type. Aiming at highlighting controversies, this article provides a critical overview of the translation of first-generation and second-generation cell types. It further emphasizes the importance of understanding the mechanisms of cardiac repair and the lessons learned from first-generation trials, in order to improve cell-based therapies and to potentially finally implement cell-free therapies.
TL;DR: Current and future research will continue to focus on the identification of haematopoietic stem cell regulators and methods for in vitro and in vivo stem cell manipulation, including genome editing, to expand the scope, potential and safety of therapy using haem atopoetic stem cells.
Abstract: The discovery and characterisation of haematopoietic stem cells has required decades of research. The identification of adult bone marrow as a source of haematopoietic cells capable of protecting an organism from otherwise lethal irradiation led to the intense search for their identity and characteristics. Using functional assays along with evolving techniques for isolation of haematopoietic cells, haematopoietic stem cell populations were able to be enriched and their characteristics analysed. The key haematopoietic stem cell characteristics of pluripotentiality and the ability for self-renewal have emerged as characteristics of several haematopoietic stem cell populations, including those that have recently challenged the conventional concepts of the haematopoietic hierarchy. Human allogeneic stem cell therapy relies on these functional characteristics of haematopoietic stem cells that can be isolated from peripheral blood, bone marrow or cord blood, with the additional requirement that immunological barriers need to be overcome to allow sustained engraftment while minimising risk of graft-versus-host disease developing in the recipient of transplanted stem cells. Current and future research will continue to focus on the identification of haematopoietic stem cell regulators and methods for in vitro and in vivo stem cell manipulation, including genome editing, to expand the scope, potential and safety of therapy using haematopoietic stem cells.
TL;DR: It is demonstrated that co-culturing EPCs with MSCs enhanced the expression of cluster of differentiation 31 and von Willebrand factor, which are specific markers of an endothelial phenotype, thus indicating that M SCs may influence the endothelial differentiation of EPC’s in vitro.
Abstract: Stem cell therapy is a promising treatment strategy for ischemic diseases. Mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) adhere to each other in the bone marrow cavity and in in vitro cultures. We have previously demonstrated that the adhesion between MSCs and EPCs is critical for MSC self-renewal and their multi-differentiation into osteoblasts and chondrocytes. In the present study, the influence of the indirect communication between EPCs and MSCs on the endothelial differentiation potential of EPCs was investigated, and the molecular mechanisms underlying MSC-mediated EPC differentiation were explored. The effects of vascular endothelial growth factor (VEGF), which is secreted by MSCs, on EPC differentiation via paracrine mechanisms were examined via co-culturing MSCs and EPCs. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to detect the expression of genes and proteins of interest. The present results demonstrated that co-culturing EPCs with MSCs enhanced the expression of cluster of differentiation 31 and von Willebrand factor, which are specific markers of an endothelial phenotype, thus indicating that MSCs may influence the endothelial differentiation of EPCs in vitro. VEGF appeared to be critical to this process. These findings are important for the understanding of the biological interactions between MSCs and EPCs, and for the development of applications of stem cell-based therapy in the treatment of ischemic diseases.
TL;DR: The present review captures the latest trends associated with the molecular mechanisms involved in glial tumorigenesis as well as the limitations of surgery, radiation and chemotherapy for the treatment of glioma.
Abstract: Glioma accounts for the majority of human brain tumors. With prevailing treatment regimens, the patients have poor survival rates. In spite of current development in mainstream glioma therapy, a cure for glioma appears to be out of reach. The infiltrative nature of glioma and acquired resistance substancially restrict the therapeutic options. Better elucidation of the complicated pathobiology of glioma and proteogenomic characterization might eventually open novel avenues for the design of more sophisticated and effective combination regimens. This could be accomplished by individually tailoring progressive neuroimaging techniques, terminating DNA synthesis with prodrug-activating genes, silencing gliomagenesis genes (gene therapy), targeting miRNA oncogenic activity (miRNA-mRNA interaction), combining Hedgehog-Gli/Akt inhibitors with stem cell therapy, employing tumor lysates as antigen sources for efficient depletion of tumor-specific cancer stem cells by cytotoxic T lymphocytes (dendritic cell vaccination), adoptive transfer of chimeric antigen receptor-modified T cells, and combining immune checkpoint inhibitors with conventional therapeutic modalities. Thus, the present review captures the latest trends associated with the molecular mechanisms involved in glial tumorigenesis as well as the limitations of surgery, radiation and chemotherapy. In this article we also critically discuss the next generation molecular therapeutic strategies and their mechanisms for the successful treatment of glioma.
TL;DR: 3D cell printing can overcome the current concerns of stem cell therapy by delivering the 3D construct to the damaged site by solving the in vivo and in vitro tracking and monitoring of the performance of 3D cell printed tissue in a noninvasive and real-time manner.
Abstract: Stem cell theranostics has received much attention for noninvasively monitoring and tracing transplanted therapeutic stem cells through imaging agents and imaging modalities. Despite the excellent regenerative capability of stem cells, their efficacy has been limited due to low cellular retention, low survival rate, and low engraftment after implantation. Three-dimensional (3D) cell printing provides stem cells with the similar architecture and microenvironment of the native tissue and facilitates the generation of a 3D tissue-like construct that exhibits remarkable regenerative capacity and functionality as well as enhanced cell viability. Thus, 3D cell printing can overcome the current concerns of stem cell therapy by delivering the 3D construct to the damaged site. Despite the advantages of 3D cell printing, the in vivo and in vitro tracking and monitoring of the performance of 3D cell printed tissue in a noninvasive and real-time manner have not been thoroughly studied. In this review, we explore the recent progress in 3D cell technology and its applications. Finally, we investigate their potential limitations and suggest future perspectives on 3D cell printing and stem cell theranostics.
TL;DR: Extracellular matrix/stromal vascular fraction gel derived from lipoaspirate is an autologous injectable derived from native extracellular Matrix and is a functional cellular component generated using a simple mechanical process that may offer a novel mode of tissue repair suitable for clinical application in stem cell therapies.
Abstract: Background:Adipose-derived stem cells and other stromal vascular fraction cells were used more often for stem cell therapy, even though limitations such as poor cell retention rate, complicated and expensive isolation processes, and the use of specific laboratory equipment need to be overcome.Method
TL;DR: Application of a prefabricated cardiac tissue patch to prevent dilation and to improve pumping efficiency of the infarcted heart offers a promising strategy for making stem cell therapy a clinical reality.
TL;DR: The recent advances in understanding the regulatory effects of stem cells secreted factors on different immune cells including macrophages, dendritic cells, neutrophils, NK cells, T cells, and B cells are summarized.
TL;DR: The some biological features are the main factors that impact the regenerative activity of ADSCs, including the modulation of the cellular immune system properties and secretion of bioactive proteins such as cytokines, chemokines and growth factors, as well as their intrinsic anti-ulcer and anti-inflammatory potential.
Abstract: The application of appropriate cell origin for utilizing in regenerative medicine is the major issue. Various kinds of stem cells have been used for the tissue engineering and regenerative medicine. Such as, several stromal cells have been employed as treat option for regenerative medicine. For example, human bone marrow-derived stromal cells and adipose-derived stromal cells (ADSCs) are used in cell-based therapy. Data relating to the stem cell therapy and processes associated with ADSC has developed remarkably in the past 10 years. As medical options, both the stromal vascular and ADSC suggests good opportunity as marvelous cell-based therapeutics. The some biological features are the main factors that impact the regenerative activity of ADSCs, including the modulation of the cellular immune system properties and secretion of bioactive proteins such as cytokines, chemokines and growth factors, as well as their intrinsic anti-ulcer and anti-inflammatory potential. A variety of diseases have been treated by ADSCs, and it is not surprising that there has been great interest in the possibility that ADSCs might be used as therapeutic strategy to improve a wider range of diseases. This is especially important when it is remembered that routine therapeutic methods are not completely effective in treat of diseases. Here, it was discuss about applications of ADSC to colitis, liver failure, diabetes mellitus, multiple sclerosis, orthopaedic disorders, hair loss, fertility problems, and salivary gland damage.
TL;DR: The results indicated that the transplantation of allogeneic ADSCs via the hydrogel improves the efficiency of cell delivery and optimizes the performance of ADSCs for augmenting diabetic wound healing and may provide a novel therapeutic strategy for the treatment of nonhealing diabetic foot ulcers.
01 Sep 2017
TL;DR: Safety concerns are still a primary hurdle for stem cell therapy, and thromboembolism as a critical complication should be prevented appropriately.
Abstract: Objective To investigate the thromboembolism induced by blood-mediated inflammatory reactions against infused cells during the clinical application of stem cells. Methods Two patients with renal transplantation and chronic kidney disease, respectively, experienced thromboembolism after umbilical cord mesenchymal stem cell (UCMSC) infusion. The clinical manifestations and the laboratory test results were collected and analyzed. Results The patients received stem cell infusion through the peripheral veins and presented with a swollen and painful forearm postinfusion. Doppler ultrasound showed venous clots at the proximal end of the puncture site. Urokinase and warfarin were used for thrombolytic therapy. The swelling and pain were relieved and cured. Conclusion Safety concerns are still a primary hurdle for stem cell therapy, and thromboembolism as a critical complication should be prevented appropriately.
TL;DR: The results suggest that epicardial transplantation of the cell patch promotes repair of the infarcted myocardium and improves cardiac functions by enhancing the survival of the transplanted cells, accelerating locality paracrine, and then activating the epicardium and recruiting endogenous c‐kit+ cells.
Abstract: Cardiac patch is considered a promising strategy for enhancing stem cell therapy of myocardial infarction (MI). However, the underlying mechanisms for cardiac patch repairing infarcted myocardium remain unclear. In this study, we investigated the mechanisms of PCL/gelatin patch loaded with MSCs on activating endogenous cardiac repair. PCL/gelatin patch was fabricated by electrospun. The patch enhanced the survival of the seeded MSCs and their HIF-1α, Tβ4, VEGF and SDF-1 expression and decreased CXCL14 expression in hypoxic and serum-deprived conditions. In murine MI models, the survival and distribution of the engrafted MSCs and the activation of the epicardium were examined, respectively. At 4 weeks after transplantation of the cell patch, the cardiac functions were significantly improved. The engrafted MSCs migrated across the epicardium and into the myocardium. Tendency of HIF-1α, Tβ4, VEGF, SDF-1 and CXCL14 expression in the infarcted myocardium was similar with expression in vitro. The epicardium was activated and epicardial-derived cells (EPDCs) migrated into deep tissue. The EPDCs differentiated into endothelial cells and smooth muscle cells, and some of EPDCs showed to have differentiated into cardiomyocytes. Density of blood and lymphatic capillaries increased significantly. More c-kit+ cells were recruited into the infarcted myocardium after transplantation of the cell patch. The results suggest that epicardial transplantation of the cell patch promotes repair of the infarcted myocardium and improves cardiac functions by enhancing the survival of the transplanted cells, accelerating locality paracrine, and then activating the epicardium and recruiting endogenous c-kit+ cells. Epicardial transplantation of the cell patch may be applied as a novel effective MI therapy.
TL;DR: It seems that chemical and pharmacological preconditioning enhances their therapeutic efficacy in cell therapy, and effects of all‐trans retinoic acid (ATRA) on survival, angiogenesis and migration of mesenchymal stem cells in vitro and in a wound‐healing model.
Abstract: Objectives
Stem cell therapy is considered to be a suitable alternative in treatment of a number of diseases. However, there are challenges in their clinical application in cell therapy, such as to reduce survival and loss of transplanted stem cells. It seems that chemical and pharmacological preconditioning enhances their therapeutic efficacy. In this study, we investigated effects of all-trans retinoic acid (ATRA) on survival, angiogenesis and migration of mesenchymal stem cells (MSCs) in vitro and in a wound-healing model.
Materials and methods
MSCs were treated with a variety of concentrations of ATRA, and mRNA expression of cyclo-oxygenase-2 (COX-2), hypoxia-inducible factor-1 (HIF-1), C-X-C chemokine receptor type 4 (CXCR4), C-C chemokine receptor type 2 (CCR2), vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) and Ang-4 were examined by qRT-PCR. Prostaglandin E2 (PGE2) levels were measured using an ELISA kit and MSC angiogenic potential was evaluated using three-dimensional tube formation assay. Finally, benefit of ATRA-treated MSCs in wound healing was determined with a rat excisional wound model.
Results
In ATRA-treated MSCs, expressions of COX-2, HIF-1, CXCR4, CCR2, VEGF, Ang-2 and Ang-4 increased compared to control groups. Overexpression of the related genes was reversed by celecoxib, a selective COX-2 inhibitor. Tube formation and in vivo wound healing of ATRA-treated MSCs were also significantly enhanced compared to untreated MSCs.
Conclusion
Pre-conditioning of MSCs with ATRA increased efficacy of cell therapy by activation of survival signalling pathways, trophic factors and release of pro-angiogenic molecules.
TL;DR: In vitro experimental outcomes showed the differentiation potential and potent paracrine effect of P-MSCs, which led to the acceleration of ischemia recovery, due to newly formed capillaries, increased arterioles, and secretion of various proangiogenic factors.
TL;DR: The iPSC-NP treatment of spinal cord injury (SCI) provided the highest recovery of locomotor function due to robust graft survival and its effect on tissue sparing, reduction of glial scarring, and increased axonal sprouting.
TL;DR: Li-ESWT activation of local penile progenitor cells might be one of the mechanisms that contribute to the beneficial effects of shockwave treatment for erectile dysfunction, which represents a non-invasive alternative to exogenous stem cell therapy.
TL;DR: The results suggest that the presence of embryonic and proliferation markers even in late passage may potentially endorse the application of dental-derived MSCs in stem cell therapy-based clinical trials.
Abstract: Background. Neural crest-derived mesenchymal stem cells (MSCs) from human oral tissues possess immunomodulatory and regenerative properties and are emerging as a potential therapeutic tool to treat diverse diseases, such as multiple sclerosis, myocardial infarction, and connective tissue damages. In addition to cell-surface antigens, dental MSCs express embryonic stem cell markers as neural crest cells originate from the ectoderm layer. In vitro passages may eventually modify these embryonic marker expressions and other stemness properties, including proliferation. In the present study, we have investigated the expression of proteins involved in cell proliferation/senescence and embryonic stem cell markers during early (passage 2) and late passages (passage 15) in MSCs obtained from human gingiva, periodontal, and dental pulp tissues. Methods. Cell proliferation assay, beta galactosidase staining, immunocytochemistry, and real-time PCR techniques were applied. Results. Cell proliferation assay showed no difference between early and late passages while senescence markers p16 and p21 were considerably increased in late passage. Embryonic stem cell markers including SKIL, MEIS1, and JARID2 were differentially modulated between P2 and P15 cells. Discussion. Our results suggest that the presence of embryonic and proliferation markers even in late passage may potentially endorse the application of dental-derived MSCs in stem cell therapy-based clinical trials.
TL;DR: It is shown here that high-speed MRI can be used to visualize the intravascular distribution of a superparamagnetic iron oxide contrast agent and can thus beused to accurately predict the distribution of intra-arterial administered stem cells.
Abstract: Stem cell therapy for neurological disorders reached a pivotal point when the efficacy of several cell types was demonstrated in small animal models. Translation of stem cell therapy is contingent upon overcoming the challenge of effective cell delivery to the human brain, which has a volume ∼1000 times larger than that of the mouse. Intra-arterial injection can achieve a broad, global, but also on-demand spatially targeted biodistribution; however, its utility has been limited by unpredictable cell destination and homing as dictated by the vascular territory, as well as by safety concerns. We show here that high-speed MRI can be used to visualize the intravascular distribution of a superparamagnetic iron oxide contrast agent and can thus be used to accurately predict the distribution of intra-arterial administered stem cells. Moreover, high-speed MRI enables the real-time visualization of cell homing, providing the opportunity for immediate intervention in the case of undesired biodistribution.