Regenerative Stem Cell Therapy Research Articles

A Preliminary Computational Investigation Into the Flow of PEG in Rat Myocardial Tissue for Regenerative Therapy.

Myocardial infarction (MI), a type of cardiovascular disease, affects a significant proportion of people around the world. Traditionally, non-communicable chronic diseases were largely associated with aging populations in higher income countries. It is now evident that low- to middle-income countries are also affected and in these settings, younger individuals are at high risk. Currently, interventions for MI prolong the time to heart failure. Regenerative medicine and stem cell therapy have the potential to mitigate the effects of MI and to significantly improve the quality of life for patients. The main drawback with these therapies is that many of the injected cells are lost due to the vigorous motion of the heart. Great effort has been directed toward the development of scaffolds which can be injected alongside stem cells, in an attempt to improve retention and cell engraftment. In some cases, the scaffold alone has been seen to improve heart function. This study focuses on a synthetic polyethylene glycol (PEG) based hydrogel which is injected into the heart to improve left ventricular function following MI. Many studies in literature characterize PEG as a Newtonian fluid within a specified shear rate range, on the macroscale. The aim of the study is to characterize the flow of a 20 kDa PEG on the microscale, where the behavior is likely to deviate from macroscale flow patterns. Micro particle image velocimetry (μPIV) is used to observe flow behavior in microchannels, representing the gaps in myocardial tissue. The fluid exhibits non-Newtonian, shear-thinning behavior at this scale. Idealized two-dimensional computational fluid dynamics (CFD) models of PEG flow in microchannels are then developed and validated using the μPIV study. The validated computational model is applied to a realistic, microscopy-derived myocardial tissue model. From the realistic tissue reconstruction, it is evident that the myocardial flow region plays an important role in the distribution of PEG, and therefore, in the retention of material.

Mesenchymal stem cells for sensorineural hearing loss: protocol for a systematic review of preclinical studies

BackgroundSensorineural hearing loss (SNHL) is the most common form of hearing impairment and is characterized by a loss of receptor hair cells and/or spiral ganglion neurons. Regenerative stem cell therapy could potentially restore normal hearing and slow the progression of hearing loss in patients. Preclinical animal studies have demonstrated that mesenchymal stem cells (MSCs) could be a promising new therapy for this condition. These findings have prompted investigators to begin human clinical trials to assess the safety and efficacy of MSCs for the treatment of SNHL. The objective of the proposed systematic review is to examine the efficacy of MSCs as a therapy for SNHL in animal models.MethodsWe will include preclinical animal studies of SNHL in which MSCs are administered, and outcomes are compared against MSC-naïve controls. The primary outcome will include audiologic tests that are routinely used in experimental studies of hearing loss, such as auditory brainstem response (ABR) and distortion product otoacoustic emissions testing (DPOAE). Secondary outcomes will include histology, microscopy, gene protein expression, and behavioral responses of animals. Electronic searches of MEDLINE via PubMed, Scopus, ScienceDirect, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) will be performed. Search results will be screened independently and in duplicate. Data from eligible studies will be extracted, pooled, and analyzed using random effects models. Risk of bias and publication bias will be assessed using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk of bias tool and Funnel Plots/Egger’s regression tests, respectively.DiscussionThis systematic review will provide a summary of the efficacy of MSC therapy in animal models of SNHL, utilizing functional hearing assessment as a primary outcome. Findings from this review are important because they can elucidate research gaps that should be addressed in future preclinical studies and in turn can be translated into clinical studies.Systematic review registrationCAMARADES (http://www.dcn.ed.ac.uk/camarades/)

Advances in Regenerative Stem Cell Therapy in Androgenic Alopecia and Hair Loss: Wnt pathway, Growth-Factor, and Mesenchymal Stem Cell Signaling Impact Analysis on Cell Growth and Hair Follicle Development.

The use of stem cells has been reported to improve hair regrowth in several therapeutic strategies, including reversing the pathological mechanisms, that contribute to hair loss, regeneration of hair follicles, or creating hair using the tissue-engineering approach. Although various promising stem cell approaches are progressing via pre-clinical models to clinical trials, intraoperative stem cell treatments with a one-step procedure offer a quicker result by incorporating an autologous cell source without manipulation, which may be injected by surgeons through a well-established clinical practice. Many authors have concentrated on adipose-derived stromal vascular cells due to their ability to separate into numerous cell genealogies, platelet-rich plasma for its ability to enhance cell multiplication and neo-angiogenesis, as well as human follicle mesenchymal stem cells. In this paper, the significant improvements in intraoperative stem cell approaches, from in vivo models to clinical investigations, are reviewed. The potential regenerative instruments and functions of various cell populaces in the hair regrowth process are discussed. The addition of Wnt signaling in dermal papilla cells is considered a key factor in stimulating hair growth. Mesenchymal stem cell-derived signaling and growth factors obtained by platelets influence hair growth through cellular proliferation to prolong the anagen phase (FGF-7), induce cell growth (ERK activation), stimulate hair follicle development (β-catenin), and suppress apoptotic cues (Bcl-2 release and Akt activation).

TUDCA-treated chronic kidney disease-derived hMSCs improve therapeutic efficacy in ischemic disease via PrPC

Although autologous human mesenchymal stem cells (hMSCs) are a promising source for regenerative stem cell therapy in chronic kidney disease (CKD), the barriers associated with pathophysiological conditions limit therapeutic applicability to patients. We confirmed that level of cellular prion protein (PrPC) in serum was decreased and mitochondria function of CKD-derived hMSCs (CKD-hMSCs) was impaired in patients with CKD. We proved that treatment of CKD-hMSCs with tauroursodeoxycholic acid (TUDCA), a bile acid, enhanced the mitochondrial function of these cells through regulation of PINK1-PrPC-dependent pathway. In a murine hindlimb ischemia model with CKD, tail vein injection of TUDCA-treated CKD-hMSCs improved the functional recovery, including kidney recovery, limb salvage, blood perfusion ratio, and vessel formation along with restored expression of PrPC in the blood serum of the mice. These data suggest that TUDCA-treated CKD-hMSCs are a promising new autologous stem cell therapeutic intervention that dually treats cardiovascular problems and CKD in patients.

Injection of Stromal Vascular Fraction Plus Platelet-Rich Plasma in a Non-Healing Decubitus Ulcer

Non-healing decubitus ulcers can be challenging to treat and may often progress to other life-threatening complications. Significant tissue damage is present in stage 3/4 wounds and treatment options can be limited or present additional risks. Applications of regenerative medicine and stem cell therapy are rapidly expanding in particular in the field of non-healing wounds. Adipose tissue is a rich source of autologous stem cells which can be easily isolated in an outpatient visit. The population of cells collected from fat after the adipocytes (fat cells) are removed via centrifugation is called stromal vascular fraction (SVF) and contains mesenchymal/adipose stem cells, fibroblasts, pericytes, endothelial/progenitor cells and more. Adipose tissue is collected under local anesthesia via cannula and SVF is separated via centrifugation after enzyme digestion. In addition, peripheral blood can be centrifuged to collect platelet-rich plasma (PRP) which contains a mixture of cytokines/growth factors. Here we present a first in man case study of a single injection of SVF and PRP into a chronic non-healing stage 3 ulcer in a patient with an incomplete spinal cord injury. After removing approximately 60 mL of fat tissue, the SVF was isolated and resuspended in approximately 5 mL of PRP for local administration in the non-healing wound. The wound was monitored and tracked with imaging and the patient was tracked for quality of life parameters as well as safety (adverse events). No complications or other safety events were reported either during the procedure or in the months following the procedure. The patient reported reduction of pain consistent with wound healing and a willingness to repeat therapies if required. The healing stage 3 pressure injury showed clear re-epithelialization. Based on this case study, a feasible treatment plan to promote healing for stage 3 and 4 decubitus ulcers could be a single injection of SVF plus PRP. J Med Cases. 2018;9(10):323-327 doi: https://doi.org/10.14740/jmc3128w

Use of Autologous Stem Cells for the Regeneration of Periodontal Defects in Animal Studies: a Systematic Review and Meta-Analysis.

ABSTRACTObjectivesTo overview preclinical animal trials and quantify the effect size that stem cell therapy has on the regeneration of periodontal tissue complex.Material and MethodsA systematic MEDLINE (PubMed) online library search was conducted for preclinical animal studies in vivo, using autologous periodontal ligament, dental pulp, cementum, alveolar periosteal, gingival margin or adipose stem cell types for periodontal tissue complex regeneration purposes. Studies had to be published between 2007.09.01 and 2017.09.01 in the English language.ResultsOnline library search yielded 2099 results. After the title, abstract and full-text screening ten studies fit inclusion criteria and were pooled into meta-analysis. Overall the stem cell regenerative therapy had a statistically significant positive influence on the periodontal tissue regeneration when compared to the control groups. The biggest influence was made to the regeneration of cementum (standardised mean difference [SMD] 2.25 [95% confidence interval (CI) = 1.31 to 3.2]) while the smallest influence was made to the alveolar bone (SMD 1.47 [95% CI = 0.7 to 2.25]) the effect size for periodontal ligament regeneration was (SMD 1.8 [95% CI = 1 to 2.59]). Subgroup analysis showed statistically significant (P < 0.05) differences between different cell types in the alveolar bone and cementum regeneration groups and in alveolar bone group in relation to scaffold materials.ConclusionsStem cell therapy has a positive impact on periodontal tissue complex regeneration. Such therapy has the biggest influence on cementum regeneration meanwhile alveolar bone regeneration is influenced by the least amount. However more and less diverse preclinical studies are needed to have a greater statistical power in future meta-analyses.

Adult Stem Cells for Regenerative Therapy.

Cell therapy has been identified as an effective method to regenerate damaged tissue. Adult stem cells, also known as somatic stem cells or resident stem cells, are a rare population of undifferentiated cells, located within a differentiated organ, in a specialized structure, called a niche, which maintains the microenvironments that regulate the growth and development of adult stem cells. The adult stem cells are self-renewing, clonogenic, and multipotent in nature, and their main role is to maintain the tissue homeostasis. They can be activated to proliferate and differentiate into the required type of cells, upon the loss of cells or injury to the tissue. Adult stem cells have been identified in many tissues including blood, intestine, skin, muscle, brain, and heart. Extensive preclinical and clinical studies have demonstrated the structural and functional regeneration capabilities of these adult stem cells, such as bone marrow-derived mononuclear cells, hematopoietic stem cells, mesenchymal stromal/stem cells, resident adult stem cells, induced pluripotent stem cells, and umbilical cord stem cells. In this review, we focus on the human therapies, utilizing adult stem cells for their regenerative capabilities in the treatment of cardiac, brain, pancreatic, and eye disorders.

Surface modification of PHBV nanofiber mats for rapid cell cultivation and harvesting

To maintain the original function of a specific tissue for therapeutic tissue engineering, an advanced cell culture surface for repeat cell proliferation is necessary. We designed a novel cell proliferation and rapid harvesting surface by combining nonwoven nanofiber mat and a thermo-responsive polymer. Nanofibrous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) mats were fabricated by the electrospinning technique. A poly(N-isopropylacrylamide) (PNIPAM) thermo-responsive layer was grafted on the PHBV nanofiber mat by electron beam irradiation. The average diameter of the PNIPAM-grafted PHBV nanofibers was determined by SEM. ATR-FTIR and ESCA were used to confirm the grafting of PNIPAM onto the PHBV nanofiber surface. Water contact angles on the mats were measured in response to temperature changes. Human adipose-derived stem cells (ADSCs) were cultured on the PNIPAM-grafted PHBV nanofiber mat to investigate cell proliferation, harvesting, and functionality during repeat subculture. Detached ADSCs from each surface by low temperature treatment and trypsin-EDTA were compared by a fluorescence-activated cell sorter (FACS) using expression of stem cell membrane-specific markers such as CD-13 PE, CD-29 PE, and CD-90 FITC. The mass cultivation and intact harvesting of stem cells by low temperature treatment using a thermo-responsive PHBV nanofiber mat is a promising technique for use in regenerative medicine and stem cell therapy.

Mechanical forces direct stem cell behaviour in development and regeneration.

Stem cells and their local microenvironment, or niche, communicate through mechanical cues to regulate cell fate and cell behaviour and to guide developmental processes. During embryonic development, mechanical forces are involved in patterning and organogenesis. The physical environment of pluripotent stem cells regulates their self-renewal and differentiation. Mechanical and physical cues are also important in adult tissues, where adult stem cells require physical interactions with the extracellular matrix to maintain their potency. In vitro, synthetic models of the stem cell niche can be used to precisely control and manipulate the biophysical and biochemical properties of the stem cell microenvironment and to examine how the mode and magnitude of mechanical cues, such as matrix stiffness or applied forces, direct stem cell differentiation and function. Fundamental insights into the mechanobiology of stem cells also inform the design of artificial niches to support stem cells for regenerative therapies.

Adipose stem cells from obese patients show specific differences in the metabolic regulators vitamin D and Gas5

Adipose tissue is a significant source of mesenchymal stem cells for regenerative therapies; however, caution should be taken as their environmental niche can affect their functional properties. We have previously demonstrated the negative impact of obesity on the function of adipose-derived stem cells (ASCs). Here we have evaluated other possible properties and targets that are altered by obesity such as the recently described long non-coding molecule Gas5, which is involved in glucocorticoid resistance. Using ASCs isolated from obese (oASCs) and control subjects (cASCs), we have analyzed additional metabolic and inflammatory conditions that could be related with their impaired therapeutic potential and consequently their possible usefulness in the clinic.

Placental stem cells: The promise of curing diseases before birth

Regenerative medicine is a rapidly expanding and promising field for many diseases and injuries. Stem cells for regenerative therapies have originally been obtained from bone marrow, but are now readily extracted from a variety of adult tissues. Fetal tissue has recently garnered interest for its ease of differentiation into a variety of phenotypes and its relative abundance of pluripotent-linked transcription factors. However, much ethical concern surrounds the methods of obtaining fetal cells. The placenta has emerged as a potential source of fetal derived cells due to its favorable technical and ethical characteristics, as well as its promising therapeutic properties. This preview focuses on providing on overview on the derivation and characteristics of placental derived stem cells as well as delving into their various clinical applications and potential future directions.

Quaking Is a Key Regulator of Endothelial Cell Differentiation, Neovascularization, and Angiogenesis

The capability to derive endothelial cell (ECs) from induced pluripotent stem cells (iPSCs) holds huge therapeutic potential for cardiovascular disease. This study elucidates the precise role of the RNA‐binding protein Quaking isoform 5 (QKI‐5) during EC differentiation from both mouse and human iPSCs (hiPSCs) and dissects how RNA‐binding proteins can improve differentiation efficiency toward cell therapy for important vascular diseases. iPSCs represent an attractive cellular approach for regenerative medicine today as they can be used to generate patient‐specific therapeutic cells toward autologous cell therapy. In this study, using the model of iPSCs differentiation toward ECs, the QKI‐5 was found to be an important regulator of STAT3 stabilization and vascular endothelial growth factor receptor 2 (VEGFR2) activation during the EC differentiation process. QKI‐5 was induced during EC differentiation, resulting in stabilization of STAT3 expression and modulation of VEGFR2 transcriptional activation as well as VEGF secretion through direct binding to the 3′ UTR of STAT3. Importantly, mouse iPS‐ECs overexpressing QKI‐5 significantly improved angiogenesis and neovascularization and blood flow recovery in experimental hind limb ischemia. Notably, hiPSCs overexpressing QKI‐5, induced angiogenesis on Matrigel plug assays in vivo only 7 days after subcutaneous injection in SCID mice. These results highlight a clear functional benefit of QKI‐5 in neovascularization, blood flow recovery, and angiogenesis. Thus, they provide support to the growing consensus that elucidation of the molecular mechanisms underlying EC differentiation will ultimately advance stem cell regenerative therapy and eventually make the treatment of cardiovascular disease a reality. The RNA binding protein QKI‐5 is induced during EC differentiation from iPSCs. RNA binding protein QKI‐5 was induced during EC differentiation in parallel with the EC marker CD144. Immunofluorescence staining showing that QKI‐5 is localized in the nucleus and stained in parallel with CD144 in differentiated ECs (scale bar = 50 µm). stem cells 2017 Stem Cells 2017;35:952–966

Efficacy and Safety of Immuno-Magnetically Sorted Smooth Muscle Progenitor Cells Derived from Human-Induced Pluripotent Stem Cells for Restoring Urethral Sphincter Function.

Human‐induced pluripotent stem cells (hiPSCs)‐based cell therapy holds promise for treating stress urinary incontinence (SUI). However, safety concerns, especially tumorgenic potential of residual undifferentiated cells in hiPSC derivatives, are major barriers for its clinical translation. An efficient, fast and clinical‐scale strategy for purifying committed cells is also required. Our previous studies demonstrated the regenerative effects of hiPSC‐derived smooth muscle progenitor cells (pSMCs) on the injured urethral sphincter in SUI, but the differentiation protocol required fluorescence‐activated cell sorting (FACS) which is not practical for autologous clinical applications. In this study, we examined the efficacy and safety of hiPSC‐derived pSMC populations sorted by FDA‐approved magnetic‐activated cell sorting (MACS) using cell‐surface marker CD34 for restoring urethral sphincter function. Although the heterogeneity of MACS‐sorted pSMCs was higher than that of FACS‐sorted pSMCs, the percentage of undifferentiated cells dramatically decreased after directed differentiation in vitro. In vivo studies demonstrated long‐term cell integration and no tumor formation of MACS‐sorted pSMCs after transplantation. Furthermore, transplantation of MACS‐sorted pSMCs into immunodeficient SUI rats was comparable to transplantation with FACS‐sorted pSMCs for restoration of the extracellular matrix metabolism and function of the urethral sphincter. In summary, purification of hiPSC derivatives using MACS sorting for CD34 expression represent an efficient approach for production of clinical‐scale pSMCs for autologous stem cell therapy for regeneration of smooth muscle tissues. Stem Cells Translational Medicine 2017;6:1158–1167

Pharmacological inhibition of DNA methyltransferase 1 promotes neuronal differentiation from rodent and human nasal olfactory stem/progenitor cell cultures

Nasal olfactory stem and neural progenitor cells (NOS/PCs) are considered possible tools for regenerative stem cell therapies in neurodegenerative diseases. Neurogenesis is a complex process regulated by extrinsic and intrinsic signals that include DNA-methylation and other chromatin modifications that could be experimentally manipulated in order to increase neuronal differentiation. The aim of the present study was the characterization of primary cultures and consecutive passages (P2–P10) of NOS/PCs isolated from male Swiss-Webster (mNOS/PCs) or healthy humans (hNOS/PCs). We evaluated and compared cellular morphology, proliferation rates and the expression pattern of pluripotency-associated markers and DNA methylation-associated gene expression in these cultures. Neuronal differentiation was induced by exposure to all-trans retinoic acid and forskolin for 7 days and evaluated by morphological analysis and immunofluorescence against neuronal markers MAP2, NSE and MAP1B. In response to the inductive cues mNOS/PCs expressed NSE (75.67%) and MAP2 (35.34%); whereas the majority of the hNOS/PCs were immunopositive to MAP1B. Treatment with procainamide, a specific inhibitor of DNA methyltransferase 1 (DNMT1), increases in the number of forskolin‘/retinoic acid-induced mature neuronal marker-expressing mNOS/PCs cells and enhances neurite development in hNOS/PCs. Our results indicate that mice and human nasal olfactory stem/progenitors cells share pluripotency-related gene expression suggesting that their application for stem cell therapy is worth pursuing and that DNA methylation inhibitors could be efficient tools to enhance neuronal differentiation from these cells.

Icaritin enhances mESC self-renewal through upregulating core pluripotency transcription factors mediated by ER\u03b1

Utilization of small molecules in modulation of stem cell self-renewal is a promising approach to expand stem cells for regenerative therapy. Here, we identify Icaritin, a phytoestrogen molecule enhances self-renewal of mouse embryonic stem cells (mESCs). Icaritin increases mESCs proliferation while maintains their self-renewal capacity in vitro and pluripotency in vivo. This coincides with upregulation of key pluripotency transcription factors OCT4, NANOG, KLF4 and SOX2. The enhancement of mESCs self-renewal is characterized by increased population in S-phase of cell cycle, elevation of Cylin E and Cyclin-dependent kinase 2 (CDK2) and downregulation of p21, p27 and p57. PCR array screening reveals that caudal-related homeobox 2 (Cdx2) and Rbl2/p130 are remarkably suppressed in mESCs treated with Icaritin. siRNA knockdown of Cdx2 or Rbl2/p130 upregulates the expression of Cyclin E, OCT4 and SOX2, and subsequently increases cell proliferation and colony forming efficiency of mESCs. We then demonstrate that Icaritin co-localizes with estrogen receptor alpha (ERα) and activates its nuclear translocation in mESCs. The promotive effect of Icaritin on cell cycle and pluripotency regulators are eliminated by siRNA knockdown of ERα in mESCs. The results suggest that Icaritin enhances mESCs self-renewal by regulating cell cycle machinery and core pluripotency transcription factors mediated by ERα.

Mesenchymal Stem Cells in Regenerative Therapy of the Nervous System

Author(s): Yanez, Jose | Abstract: Mesenchymal stem cells (MSCs) are a form of stem cell found in bone marrow and can help aid with neurological damages. Not much is known about it in terms of risks but it has been found to renew damaged cells by replacing them with new ones in both central and peripheral nervous systems. Studies have been conducted on rats that have suffered cerebral ischemia which is lack of blood flow to the brain. Only those that contained a high rating of cerebral ischemia such as being brain dead were excluded in the experiment to ensure proper results. It was found that rats with the disease that suffered minor damages were able to repair their neurons with MSCs therapy. Rats that were not brain dead but suffered extreme brain damage unfortunately were not able to properly regenerate neurological damage done. MSCs contain potential in becoming a beneficial and new form of regenerative medicine to help aid with neurological damage caused by diseases.

Adult Stem Cell Therapy and Heart Failure, 2000 to 2016: A Systematic Review.

Stem cell therapy is a promising treatment strategy for patients with heart failure, which accounts for more than 10% of deaths in the United States annually. Despite more than a decade of research, further investigation is still needed to determine whether stem cell regenerative therapy is an effective treatment strategy and can be routinely implemented in clinical practice. To describe the progress in cardiac stem cell regenerative therapy using adult stem cells and to highlight the merits and limitations of clinical trials performed to date. Information for this review was obtained through a search of PubMed and the Cochrane database for English-language studies published between January 1, 2000, and July 26, 2016. Twenty-nine randomized clinical trials and 7 systematic reviews and meta-analyses were included in this review. Although adult stem cells were once believed to have the ability to create new heart tissue, preclinical studies suggest that these cells release cardioprotective paracrine factors that activate endogenous pathways, leading to myocardial repair. Subsequent randomized clinical trials, most of which used autologous bone marrow mononuclear cells, have found only a modest benefit in patients receiving stem cell therapy. The lack of a significant benefit may result from variations in trial methods, discrepancies in reporting, and an overreliance on surrogate end points. Although stem cell therapy for cardiovascular disease is not yet ready for routine clinical application, significant progress continues to be made. Physicians should be aware of the current status of this treatment so that they can better inform their patients who may be in search of alternative therapies.

ДО МЕТОДУ ОТРИМАННЯ МЕЗЕНХІМАЛЬНИХ СТОВБУРОВИХ КЛІТИН ВЕЛИКОЇ РОГАТОЇ ХУДОБИ

Prospects receipt and use of multipotent mesenchymal stem cells of an adult organism, determined by their basic properties and characteristics. Diploid cell cultures derived from mammalian tissues and organs, preserve their species and tissue specificity, but have a limited period of proliferation because of aging. Therefore, the use of mesenchymal stem cells is important. The ease of selection and availability of biological material makes them today to date, the most promising cell system. Studying the properties of stem cells in veterinary medicine has its own characteristics. They are in particular, taking into account specific characteristics of the cell material, which is important in practical veterinary regenerative therapy. There is a significant amount of minutes of culturing mesenchymal stem cells, but none of the authors do not focuses on the expression of biological properties of these cells by culturing. In the study of the biological properties of mesenchymal stem cells, there are many mysteries and the unknown, but today conducted preclinical and clinical studies for the introduction of these cells to correct the damaged organs and tissues of an animal body. Thus, the study and knowledge of the underlying mechanisms that form the specific features of the biological properties of stem cells in cattle is important and urgent to develop scientifically based methods of use of mesenchymal stem cells in regenerative therapy of breast diseases in cows. Because of this work was perfected method of cultivation and crop deep freeze multipotent mesenchymal stem cells isolated from bone marrow of cattle. In studies we used mesenchymal stem cells derived from bone marrow of healthy donor cows. For bone marrow, we used our improved method. Comparative analysis of the efficiency of the allocation of mesenchymal stem cells using heparin or sodium citrate indicates no significant differences and can be used both drugs. When cultured mesenchymal stem cells by cell separation density gradient fikola is more efficient, while the second method also can be. The proposed method of obtaining and culturing multipotent mesenchymal stem cells isolated from bone marrow of cattle makes it possible to obtain stem cells with high biological activity.

Mesenchymal Stem Cell Therapy for the Treatment of Vocal Fold Scarring: A Systematic Review of Preclinical Studies.

ObjectivesTherapy with mesenchymal stem cells exhibits potential for the development of novel interventions for many diseases and injuries. The use of mesenchymal stem cells in regenerative therapy for vocal fold scarring exhibited promising results to reduce stiffness and enhance the biomechanical properties of injured vocal folds. This study evaluated the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring.Data SourcesPubMed, Embase, the Cochrane Library and Google Scholar were searched.MethodsControlled studies that assessed the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring were included. Primary outcomes were viscoelastic properties and mucosal wave amplitude.ResultsSeven preclinical animal studies (n = 152 single vocal folds) were eligible for inclusion. Evaluation of viscoelastic parameters revealed a decreased dynamic viscosity (η’) and elastic modulus (G’), i.e., decreased resistance and stiffness, in scarred vocal folds treated with mesenchymal stem cells compared to non-treated scarred vocal folds. Mucosal wave amplitude was increased in scarred vocal folds treated with mesenchymal stem cells vs. non-treated scarred vocal folds.ConclusionThe results from these studies suggest an increased regenerative effect of therapy with mesenchymal stem cells for scarred vocal folds and are encouraging for further clinical studies.

Potential Strategies to Address the Major Clinical Barriers Facing Stem Cell Regenerative Therapy for Cardiovascular Disease

ImportanceAlthough progress continues to be made in the field of stem cell regenerative medicine for the treatment of cardiovascular disease, significant barriers to clinical implementation still exist.ObjectivesTo summarize the current barriers to the clinical implementation of stem cell therapy in patients with cardiovascular disease and to discuss potential strategies to overcome them.Evidence ReviewInformation for this review was obtained through a search of PubMed and the Cochrane database for English-language studies published between January 1, 2000, and July 25, 2016. Ten randomized clinical trials and 8 systematic reviews were included.FindingsOne of the major clinical barriers facing the routine implementation of stem cell therapy in patients with cardiovascular disease is the limited and inconsistent benefit observed thus far. Reasons for this finding are unclear but may be owing to poor cell retention and survival, as suggested by numerous preclinical studies and a small number of human studies incorporating imaging to determine cell fate. Additional studies in humans using imaging to determine cell fate are needed to understand how these factors contribute to the limited efficacy of stem cell therapy. Treatment strategies to address poor cell retention and survival are under investigation and include the following: coadministration of immunosuppressive and prosurvival agents, delivery of cardioprotective factors packaged in exosomes rather than the cells themselves, and use of tissue-engineering strategies to provide structural support for cells. If larger grafts are achieved using these strategies, it will be imperative to carefully monitor for the potential risks of tumorigenicity, immunogenicity, and arrhythmogenicity.Conclusions and RelevanceDespite important achievements to date, stem cell therapy is not yet ready for routine clinical implementation. Significant research is still needed to address the clinical barriers outlined herein before the next wave of large clinical trials is under way.