Source Of Mesenchymal Stem Cells Research Articles

Sources of mesenchymal stem cells and its potential

Mesenchymal stem cells, because of their ability to differentiate along variable cell lineages and renew themselves is a topic of interest in orthopedics for their potential role in avascular necrosis of femoral head, osteoarthritis, intervertebral disc disease, ligamentous and meniscal injuries, inducing growth in osteogenesis imperfecta and gene therapy. They also possess immunosuppressive and immunomodulatory properties. Mesenchymal stem cells can be procured from different tissue sources, such as umbilical cord, synovial tissue, breast milk, menstrual blood, adipose tissue, bone marrow, dentine pulp etc. In this review, we have attempted to make a study of the recent advances in emerging new sources of mesenchymal stem cells and their therapeutic potentials.

Placenta‐Derived Mesenchymal Stem Cells for Treatment of Diseases: A Clinically Relevant Source

AbstractThe placenta is an organ that is discarded after childbirth. Recently, mesenchymal stem cells (MSCs) isolated from various parts of the placenta (PMSCs) are established as a rich, allogeneic, and sustainable source of MSCs in comparison to bone marrow MSCs (BM‐MSCs). PMSCs can be banked postnatally for future autologous and allogeneic applications in the treatment of diseases. PMSCs can be categorized as an intermediary between BM‐MSCs and embryonic stem cells (ESCs) as it is devoid of adverse aspects associated with the employment of ESCs accompanied with primitive and enhanced properties in comparison to BM‐MSCs. PMSCs are employed in the treatment of various diseases including cancer, neurological, bone, and cardiovascular disorders. This utility of PMSCs is due to its superior inherent characteristics in comparison to BM‐MSCs, which renders PMSCs more attractive for clinical translation. Herein, this review describes the superior inherent characteristics of PMSCS in contrast to BM‐MSCs including accessibility, higher expansion abilities, enhanced immunomodulatory and immunosuppressive properties, ability to differentiate beyond mesodermal lineages, pathotropic and regenerative abilities, lower immunogenicity, and anti‐cancer strategy that are correlated to its therapeutic application in the treatment of various diseases including corona virus infection started in 2019 in recent preclinical and preclinical studies.

Paper 19: The Influence of Amniotic Suspension Allografts and Bone Marrow Aspirate Concentrate on Inflammation & Cartilage Matrix Metabolism in Osteoarthritic Chondrocytes

Objectives:While bone marrow aspirate concentrate (BMAC) and amniotic suspension allografts (ASA) have all garnered clinical interest for the treatment of osteoarthritis, basic science evidence supporting their use is lacking. Specifically, there is a paucity of literature on the in vitro effects of BMAC and ASA on inflammation and cartilage matrix metabolism in OA chondrocytes and synoviocytes. The purpose of this study was to evaluate the effect of BMAC and ASA on inflammation and cartilage metabolism in a model that mimics the OA intra-articular environment: a co-culture of OA cartilage explants and synoviocytes.Methods:After institutional IRB approval, 17 patients were enrolled at the time of total knee arthroplasty for donation of cartilage, synovium, and bone marrow aspirate tissue samples. All patients had Kellgren-Lawrence Stage 2 or 3. The aspirate was then be prepared and centrifuged using a standard commercially available BMAC centrifuge system, typically yielding up to 3mL of BMAC. Synoviocyte and cartilage explant co-culture systems were created using 24-well culture plates containing 0.4mm filtered inserts. Four co-culture systems were established per patient to accommodate the 2 biologic treatment groups (BMAC and ASA), one control group at 96 hours, and one baseline control cartilage group. Multiplex ELISA was used to measure concentrations of pro-inflammatory mediators interleukin – 1b (IL-1b), interleukin – 6 (IL-6), and tumor necrosis factor – alpha (TNF–a) at 96 hours. Each sample was measured in duplicate to ensure accuracy. Additionally, both chondrocyte and synoviocyte RNA were assayed for collagen type I a1 (COL1A1), collagen type II a1 (COL2A1), collagen type III a1 (COL3A1), aggrecan (ACAN), and cartilage oligomeric matrix protein (COMP). All statistical analyses were performed on STATA v16.1. Normality of data was determined by Shapiro-Wilk test, and non-parametric or parametric tests were utilized where appropriate.Results:There were no significant differences in cytokine concentration between the 96-hr control group and the BMAC co-culture for any cytokine, although IL-6 was trending towards significance (Control: 856.3 ± 346.2 vs BMAC: 662.3 ± 346.8, p=.08). There was a significantly lower concentration of IL-1B in the ASA group compared to the control group (ASA: 11.2 ± 13.9 vs Control: 20.2 ± 39.5, p=.04) (Table 1). No significant differences in expression were observed for Col1A1, Col2A1, Col3A1, COMP or ACAN in either cartilage or synovium samples across the three groups.Conclusions:The early results from this study suggest that ASA may have anti-inflammatory properties and promote the expression of major extracellular matrix genes in both osteoarthritic chondrocytes and synoviocytes involved in cartilage matrix metabolism. Specifically, ASA was associated with decreased concentrations of IL-1ß. The use of intra-articular therapies as sources of growth factors, anti-inflammatory mediators, and potentially mesenchymal stem cells (MSCs) for OA is rapidly evolving. MSCs have garnered significant interest due to their chondrogenic potential and promise for tissue regeneration. Two commercially available sources of MSCs are bone marrow aspirate concentrate (BMAC) and amniotic membrane. As biologics garner more attention in the clinical setting, their underlying mechanisms and efficacy in in-vitro models become important to elucidate. The results from this study provide basic science support for further clinical trials comparing ASA and BMAC to current standard of care corticosteroid injections for OA.Table 1.Luminex Assay for Cytokine Concentrations in Media

Comparative gene expression analysis of stemness between periodontal ligament and umbilical cord tissues in humans

Background/purposeDue to their regenerative potential, periodontal ligament (PDL) and umbilical cord (UBC) tissues are an attractive potential mesenchymal stem cells (MSCs) source. This study compared the expression patterns of genes related to stemness between fresh PDL and UBC tissues. Materials and methodsPDL tissues were collected from 38 permanent premolars extracted for orthodontic purposes, and UBC tissues were obtained from three newborns. Each sample was immediately frozen to prevent RNA degradation. cDNA microarray analysis, quantitative real-time polymerase chain reaction (PCR), and immunohistochemical staining were performed. Gene expression patterns associated with dental stemness (DS) and induced pluripotent stemness (iPS) were compared between PDL and UBC tissues. ResultsIn the cDNA microarray analyses, the expressions of most iPS genes were greater in the PDL than in the UBC. Meanwhile, the expressions of most DS genes were greater in the UBC than in the PDL. Quantitative real-time PCR analyses showed that the expression levels of matrix metallopeptidase 13 (MMP13), ADAM metallopeptidase domain 22 (ADAM22), vascular cell adhesion protein 1 (VCAM1), and kruppel-like factor 4 (KLF4) genes were greater in the PDL than in the UBC, while the expressions of melanoma cell adhesion molecule (MCAM) and activated leukocyte cell adhesion molecule (ALCAM) were greater in the UBC than in the PDL. ConclusionThese results suggest that UBC and PDL tissues showed slightly different expression patterns of genes related to stemness, which warrants further investigation to use these tissues for future regeneration and implantation therapies.

Comparison of Biological Features of Wild European Rabbit Mesenchymal Stem Cells Derived from Different Tissues

Although the European rabbit is an “endangered” species and a notorious biological model, the analysis and comparative characterization of new tissue sources of rabbit mesenchymal stem cells (rMSCs) have not been well addressed. Here, we report for the first time the isolation and characterization of rMSCs derived from an animal belonging to a natural rabbit population within the native region of the species. New rMSC lines were isolated from different tissues: oral mucosa (rOM-MSC), dermal skin (rDS-MSC), subcutaneous adipose tissue (rSCA-MSC), ovarian adipose tissue (rOA-MSC), oviduct (rO-MSC), and mammary gland (rMG-MSC). The six rMSC lines showed plastic adhesion with fibroblast-like morphology and were all shown to be positive for CD44 and CD29 expression (characteristic markers of MSCs), and negative for CD34 or CD45 expression. In terms of pluripotency features, all rMSC lines expressed NANOG, OCT4, and SOX2. Furthermore, all rMSC lines cultured under osteogenic, chondrogenic, and adipogenic conditions showed differentiation capacity. In conclusion, this study describes the isolation and characterization of new rabbit cell lines from different tissue origins, with a clear mesenchymal pattern. We show that rMSC do not exhibit differences in terms of morphological features, expression of the cell surface, and intracellular markers of pluripotency and in vitro differentiation capacities, attributable to their tissue of origin.

Therapeutic and clinical propositions of Mesenchymal Stem Cells(MSCs) focusing on recent trial updates

The mesenchymal stroma harbours considerable population of stem cell-like cells with differentiation and self-renewal abilities that originate from several sources like amniotic fluid, Wharton’s jelly, umbilical cord etc. Mesenchymal Stem Cells (MSCs) are most commonly found in the perivascular niche. This multipotent progenitor cells have the ability to differentiate into mesodermal cell types such as adipocytes, chondrocytes and osteocytes. MSCs can also exert significant immunosuppressive and anti-inflammatory effects by interacting with lymphocytes from both innate and adaptive immune system. MSCs of fetal origins can go through same processes as MSCs derived from elsewhere. Before senescence, they make more cell divisions than adult MSCs of bone marrow or adipose tissue. The propitious properties of mesenchymal stem cells (MSCs), such as their ability to differentiate into diverse cell lineages and their regenerative properties, have intrigued researchers, whose work has provided fascinating perspectives on cell-based therapies for wide range of diseases. MSCs have a high potential for replication in vitro. International Society for Cellular Therapy (ISCT)-based MSC isolation has resulted in heterogeneous, nonclonal stromal cell cultures containing stem cells with various multipotent characteristics, committed progenitors, and differentiated cells. Nonclonal stromal cultures which are derived from bone marrow and other tissues are presently used as sources of putative MSCs for therapeutic aims. Also, MSCs have potential to endogenously repair as well as reduce the inflammatory responses that may lead to decreased morbidity and mortality rate of COVID-19. Herein, the MSC-based clinical prospects, clarifies, the recent clinical findings, therapeutic effects of MSC and clinical trials.

Different Sources of Mesenchymal Stem Cells for Tissue Regeneration: A Guide to Identifying the Most Favorable One in Orthopedics and Dentistry Applications.

The success of regenerative medicine in various clinical applications depends on the appropriate selection of the source of mesenchymal stem cells (MSCs). Indeed, the source conditions, the quality and quantity of MSCs, have an influence on the growth factors, cytokines, extracellular vesicles, and secrete bioactive factors of the regenerative milieu, thus influencing the clinical result. Thus, optimal source selection should harmonize this complex setting and ensure a well-personalized and effective treatment. Mesenchymal stem cells (MSCs) can be obtained from several sources, including bone marrow and adipose tissue, already used in orthopedic regenerative applications. In this sense, for bone, dental, and oral injuries, MSCs could provide an innovative and effective therapy. The present review aims to compare the properties (proliferation, migration, clonogenicity, angiogenic capacity, differentiation potential, and secretome) of MSCs derived from bone marrow, adipose tissue, and dental tissue to enable clinicians to select the best source of MSCs for their clinical application in bone and oral tissue regeneration to delineate new translational perspectives. A review of the literature was conducted using the search engines Web of Science, Pubmed, Scopus, and Google Scholar. An analysis of different publications showed that all sources compared (bone marrow mesenchymal stem cells (BM-MSCs), adipose tissue mesenchymal stem cells (AT-MSCs), and dental tissue mesenchymal stem cells (DT-MSCs)) are good options to promote proper migration and angiogenesis, and they turn out to be useful for gingival, dental pulp, bone, and periodontal regeneration. In particular, DT-MSCs have better proliferation rates and AT and G-MSC sources showed higher clonogenicity. MSCs from bone marrow, widely used in orthopedic regenerative medicine, are preferable for their differentiation ability. Considering all the properties among sources, BM-MSCs, AT-MSCs, and DT-MSCs present as potential candidates for oral and dental regeneration.

Adipose-derived stem cells in the treatment of hepatobiliary diseases and sepsis.

Determination of the mesenchymal stem cells is one of the greatest and most exciting achievements that tissue engineering and regenerative medicine have achieved. Adipose-derived mesenchymal stem cells (AD-MSC) are easily isolated and cultured for a long time before losing their stem cell characteristics, which are self-renewal and pluripotency. AD-MSC are mesenchymal stem cells that have pluripotent lineage characteristics. They are easily accessible, and the fraction of stem cells in the adipose tissue lysates is highest among all other sources of mesenchymal stem cells. It is also HLA-DR negative and can be transplanted allogenically without the need for immunosuppression. These advantages have popularized its use in many fields including plastic reconstructive surgery. However, in the field of hepatology and liver transplantation, the progress is slower. AD-MSC have the potential to modulate inflammation, ameliorate ischemia-reperfusion injury, and support liver and biliary tract regeneration. These are very important for the treatment of various hepatobiliary diseases. Furthermore, the anti-inflammatory potential of these cells has paramount importance in the treatment of sepsis. We need alternative therapeutic approaches to treat end-stage liver failure. AD-MSC can provide a means of therapy to bridge to definitive therapeutic alternatives such as liver transplantation. Here we propose to review theoretic applications of AD-MSC in the treatment of hepatobiliary diseases and sepsis.

Wnt/β-catenin signaling pathway is involved in early dopaminergic differentiation of trabecular meshwork-derived mesenchymal stem cells.

Permanent degeneration and loss of dopaminergic (DA) neurons in substantia nigra is the main cause of Parkinson's disease. Considering the therapeutic application of stem cells in neurodegeneration, we sought to examine the neurogenic differentiation potential of the newly introduced neural crest originated mesenchymal stem cells (MSCs), namely, trabecular meshwork-derived mesenchymal stem cells (TM-MSCs) compared to two other sources of MSCs, adipose tissue-derived stem cells(ADSCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs). The three types of cells were therefore cultured in the presence and absence of a neural induction medium followed by the analysis of their differentiation potentials. Our results showed that TM-MSCs exhibited enhanced neural morphologies as well as higher expressions of MAP2 as the general neuron marker and Nurr-1 as an early DA marker compared to the adipose tissue-derived mesenchymal stem cells(AD-MSCs) and bone marrow-derived stem cells(BMSCs). Also, analysis of Nurr-1 immunostaining showed more intense Nurr-1 stained nuclei in the neurally induced TM-MSCs compared to those in the AD-MSCs, BMSCs, and noninduced control TM-MSCs. To examine if Wnt/beta-catenin pathway drives TM-MSCs towards a DA fate, we treated them with the Wnt agonist (CHIR, 3 μM) and the Wnt antagonist (IWP-2, 3 μM). Our results showed that the expressions of Nurr-1 and MAP2, as well as the Wnt/beta-catenin target genes, c-Myc and Cyclin D1, were significantly increased in the CHIR-treated TM-MSCs, but significantly reduced in those treated with IWP-2. Altogether, we declare firsta higher neural potency of TM-MSCs compared to the more commonly used MSCs, BMSCs and ADSCs, and secondthat Wnt/beta-catenin activation directs the neurally induced TM-MSCs towards a DA fate.

Adipose tissue-derived mesenchymal stem cells' acellular product extracellular vesicles as a potential therapy for Crohn's disease.

The breakdown of gastrointestinal tract immune homeostasis leads to Crohn's disease (CD). Mesenchymal stem cells (MSCs) have demonstrated clinical efficacy in treating CD in clinical trials, but there is little known about the mechanism of healing. Considering the critical roles of macrophage polarization in CD and immunomodulatory properties of MSCs, we sought to decipher the interaction between adipose‐derived MSCs and macrophages, including their cytokine production, regulation of differentiation, and pro‐/anti‐inflammatory function. RNA extraction and next generation sequencing was performed in adipose tissue from healthy control patients' mesentery (n = 3) and CD mesentery (n = 3). Infiltrated macrophage activation in the CD mesentery was tested, MSCs and extracellular vesicles (EVs) were isolated to compare the regulation of macrophage differentiation, cytokines production, and self‐renewal capacities in vitro. CD patients' mesentery has increased M1 macrophage polarization and elevated activation. MSCs and their derived EVs, isolated from inflamed Crohn's mesentery, leads to a rapid differentiation of monocytes to a M1‐like polarized phenotype. Conversely, MSCs and their derived EVs from healthy, non‐Crohn's patients results in monocyte polarization into a M2 phenotype; this is seen regardless of the adipose source of MSCs (subcutaneous fat, omentum, normal mesentery). EVs derived from MSCs have the ability to regulate macrophage differentiation. Healthy MSCs and their associated EVs have the ability to drive monocytes to a M2 subset, effectively reversing an inflammatory phenotype. This mechanism supports why MSCs may be an effective therapeutic in CD and highlights EVs as a novel therapeutic for further exploration.

The Therapeutic Potential of Secreted Factors from Dental Pulp Stem Cells for Various Diseases.

An alternative source of mesenchymal stem cells has recently been discovered: dental pulp stem cells (DPSCs), including deciduous teeth, which can thus comprise potential tools for regenerative medicine. DPSCs derive from the neural crest and are normally implicated in dentin homeostasis. The clinical application of mesenchymal stem cells (MSCs) involving DPSCs contains various limitations, such as high cost, low safety, and cell handling issues, as well as invasive sample collection procedures. Although MSCs implantation offers favorable outcomes on specific diseases, implanted MSCs cannot survive for a long period. It is thus considered that their mediated mechanism of action involves paracrine effects. It has been recently reported that secreted molecules in DPSCs-conditioned media (DPSC-CM) contain various trophic factors and cytokines and that DPSC-CM are effective in models of various diseases. In the current study, we focus on the characteristics of DPSC-CM and their therapeutic potential against various disorders.

Transplantation of Autologous Adipose-Derived Stem Cells for Chronic Nonhealing Wounds

<p>細胞治療是國際上廣受醫學界矚目的一種新興療法，可促進慢性困難傷口癒合。幹細胞因其獨特的生物特性，具有豐富的醫療應用潛力，其中脂肪幹細胞(ASCs)為間質幹細胞之來源之一，可透過微創手術（如：抽脂手術）從脂肪組織中取得，因其可用於促進組織再生及傷口癒合而受到關注。脂肪幹細胞再生能力的潛在機制涉及細胞分化和多種旁分泌作用，可增加膠原沉積、血管新生及減少發炎。2018年9月，衛生福利部頒布《特定醫療技術檢查檢驗醫療儀器施行或使用管理辦法》，有條件地允許6項自體細胞治療技術在臺 灣進行臨床應用，包含脂肪幹細胞應用在慢性困難傷口癒合。執行此項新興醫療技術前必須接受審查，以判定其在臨床場所及人體細胞組織優良操作規範實驗室中的安全性及執行效率，且須在脂肪組織的採集與運輸、脂肪幹細胞的分離與培養，以及細胞的運輸與移植實施標準化方案。藉由臺灣現行法規對製造自體脂肪幹細胞的嚴格品質管制，可讓脂肪幹細胞療法成為慢性困難癒合傷口病人的治療選擇之一。</p> <p> </p><p>Cell therapy is an emerging practice in the international medical community used to facilitate the healing of chronic wounds. Stem cells have exhibited potential for therapeutic applications because of their unique biological properties. Adipose-derived stem cells (ASCs) can be obtained from fat tissue through minimally invasive procedures such as liposuction. Thus, ASCs have gained attention as a source of mesenchymal stem cells, which can facilitate regeneration and wound healing. The mechanism underlying the regenerative properties of ASCs involves cell differentiation and several paracrine effects, which increases collagen deposition, causes angiogenesis, and prevents inflammatory states. In September 2018, the Ministry of Health and Welfare issued the Regulations Governing the Application or Use of Specific Medical Techniques or Examinations, which conditionally allow for the clinical application of six autologous cell therapy technologies in Taiwan. The clinical use of ASCs for chronic nonhealing wounds is included. This novel medical technology must be investigated to determine its safety and efficiency in both clinical facilities and good tissue practice labs. Standardized protocols, including those for fat tissue harvest and transportation, ASC isolation and expansion, and cell transportation and transplantation, should be implemented throughout the process. With stringent quality control for autologous ASC generation in compliance with regulations in Taiwan, ASC-based therapy can be a promising treatment option for chronic nonhealing wounds.</p> <p> </p>

Isolation and Characterization of Synovial Mesenchymal Stem Cells Derived From Patients With Chronic Lateral Ankle Instability: A Comparative Analysis of Synovial Fluid, Adipose Synovium, and Fibrous Synovium of the Ankle Joint.

Background:Synovial mesenchymal stem cells (MSCs) have high proliferative potential and are considered an excellent source for stem cell therapy.Purposes:To isolate MSCs from the synovium of ankle joints in patients with chronic lateral ankle instability (CLAI) and to compare the characteristics of MSCs derived from the synovium anterior to the talus with those from the surrounding anterior talofibular ligament (ATFL) synovium.Study Design:Controlled laboratory study.Methods:The synovium was harvested from 2 locations in the ankle, the synovium anterior to the talus and the surrounding ATFL synovium, of 14 patients who underwent arthroscopic ATFL repair for CLAI without osteochondral lesions of the talus (OLTs). Synovial fluid was also harvested. MSCs were isolated from both types of synovial tissue, as well as synovial fluid. The number of MSCs in the synovium and their viability, proliferation, colony-forming units, and potential to differentiate into adipose, bone, and cartilage tissues were determined and compared between groups. Additionally, real-time polymerase chain reaction was used to assess the differentiation capacity of adipose, bone, and cartilage tissues from both samples. The Wilcoxon signed rank test was used to compare the sample weight, number of colonies, number of nucleated cells per colony, yield obtained, and phenotypic characteristics of MSCs derived from different locations of the synovium.Results:No significant differences were observed in the sample weight (P = .051), number of nucleated cells per milligram (P = .272), number of colonies (P = .722), and yield obtained (P = .099) between the 2 groups. MSCs could not be isolated from synovial fluid. The frequency of oil red O–positive adipogenic colonies (P = .028) and the expression of the adipsin gene (P < .05) were significantly increased in the cells from the synovium anterior to the talus compared to those in the cells from the surrounding ATFL synovium. However, chondrogenic and osteogenic potentials were not significantly different between the 2 groups.Conclusion:Synovial MSCs obtained from the ankle joint had self-renewal and multilineage differentiation potential, although the adipogenesis potential of MSCs from the synovium anterior to the talus was superior to that from the surrounding ATFL synovium.Clinical Relevance:Both the adipose synovium and fibrous synovium in the ankle joints of patients with CLAI may be a good source of MSCs for stem cell therapy applications, whereas synovial fluid appeared unsuitable.

Lateral Mesoderm-Derived Mesenchymal Stem Cells With Robust Osteochondrogenic Potential and Hematopoiesis-Supporting Ability.

Mesenchymal stem cells (MSCs) are among the most promising cell sources for the treatment of various diseases. Nonetheless, the therapeutic efficacy in clinical trials has been inconsistent due to the heterogeneity of MSCs, which may be partially attributed to their undefined developmental origins. The lateral mesoderm is also a developmental source of MSCs that constitute appendicular skeletal elements in the developing vertebrate embryo. However, it is difficult to isolate homogeneous lateral mesoderm (LM)-derived MSCs from bone tissues or bone marrow due to the lack of understanding of their characteristics. Herein, we successfully established an efficient differentiation protocol for the derivation of MSCs with a LM origin from human pluripotent stem cells (hPSCs) under specific conditions. LM-MSCs resembled bone marrow-derived MSCs (BMSCs) with regard to cell surface markers, global gene profiles, and immunoregulatory activity and showed a homeodomain transcription factor (HOX) gene expression pattern typical of skeletal MSCs in long bones. Moreover, we demonstrated that LM-MSCs had an increased osteogenic/chondrogenic differentiation capacity and hematopoietic support potential compared to BMSCs. These homogeneous LM-MSCs may serve as a powerful tool for elucidating their precise role in bone formation and hematopoiesis and could be a potentially ideal cell source for therapeutic applications.

Mesenchymal Stem Cells From Different Sources in Meniscus Repair and Regeneration.

Meniscus damage is a common trauma that often arises from sports injuries or menisci tissue degeneration. Current treatment methods focus on the repair, replacement, and regeneration of the meniscus to restore its original function. The advance of tissue engineering provides a novel approach to restore the unique structure of the meniscus. Recently, mesenchymal stem cells found in tissues including bone marrow, peripheral blood, fat, and articular cavity synovium have shown specific advantages in meniscus repair. Although various studies explore the use of stem cells in repairing meniscal injuries from different sources and demonstrate their potential for chondrogenic differentiation, their meniscal cartilage-forming properties are yet to be systematically compared. Therefore, this review aims to summarize and compare different sources of mesenchymal stem cells for meniscal repair and regeneration.

A Case of Non-Progressive Congenital Myopathy: Efficacy and Clinical Outcomes of The Wharton's Jelly Derived Mesenchymal Stem Cell Transplantation

Non-Progressive Congenital Myopathy is a disease characterized by muscle weakness, and unfortunately, there is no conventional treatment. In the last decade, regenerative medicine practices have become a rising value, and Mesenchymal Stem Cells (MSCs) have fascinating outcomes in regenerative medicine with their high regenerative capacities, their ability to regulate with paracrine secretions, and their immunological properties. Based on our experience in our previous clinical studies, Wharton's-Jelly-derived (WJ-)MSCs are the most suitable source for muscle diseases among all MSC sources. In this study, we evaluated the outcomes of 10 doses of WJ-MSC transplantation to the patient diagnosed with Non-Progressive Congenital Myopathy. A 17-year-old female with a SPEN-1 mutation, Non-Progressive Congenital Myopathy patient received 10 times as 1×10⁶/kg in the intra-arterial, intramuscular and intravenous administration of allogenic WJ-MSC. Before and after the treatment, the patient was followed-up with the upper extremity scale, Vignos lower extremity scale, muscle strength scale, functional independence measure, and evaluation of Serum creatine kinase (CK) levels. Improvement in both upper extremity scale and Vignos lower extremity scales, increasing in muscle strength, and decreasing in CK-level were detected. Although transplantation of WJ-MSC cannot treat any genetic-based diseases, they may benefit in alleviating clinical outcomes of disease. More importantly, WJ-MSC transplantation may offer a better quality of life by alleviating the symptoms of this rare disease with no treatment option that can be provided in conventional methods.

The Phenotype of the Adipocytes Derived from Subcutaneous and Visceral ADMSCs Is Altered When They Originate from Morbidly Obese Women: Is There a Memory Effect?

Adipose tissue is an abundant source of mesenchymal stem cells (ADMSCs). Evidence has suggested that depot-specific ADMSCs (obtained from subcutaneous or visceral adipose tissue–subADMSCs or visADMSCs, respectively) account for differential responses of each depot to metabolic challenges. However, little is known about the phenotype and changes in metabolism of the adipocytes derived from ADMSCs of obese individuals. Therefore, we investigated the phenotypic and metabolic characteristics, particularly the lipid profile, of fully differentiated adipocytes derived from ADMSCs of lean and obese (with/without metabolic syndrome) postmenopausal women. We observed a depot-specific pattern, with more pronounced changes present in the adipocytes obtained from subADMSCs. Namely, chronic oversupply of fatty acids (present in morbid obesity) triggered an increase in CD36/SR-B2 and FATP4 protein content (total and cell surface), which translated to an increased LCFA influx (3H-palmitate uptake). This was associated with the accumulation of TAG and DAG in these cells. Furthermore, we observed that the adipocytes of visADMSCs origin were larger and showed smaller granularity than their counterparts of subADMSCs descent. Although ADMSCs were cultured in vitro, in a fatty acids-deprived environment, obesity significantly influenced the functionality of the progenitor adipocytes, suggesting the existence of a memory effect.

A systematic review on the role of MSC-derived exosomal miRNAs in the treatment of heart failure.

Heart failure (HF) is a deeply serious clinical problem that remains unsolved. Many reports highlight the cardioprotective properties of mesenchymal stem cells (MSCs), the factors contained in their secretome being particularly important for this function; these include the exosomal miRNAs (exo-miRNAs) secreted with or without stimulus which can modulate various biological processes. In search of new paradigms in heart failure, we wondered whether MSC-derived exosomal microRNAs could play a role in the management of clinical patients. To analyze whether there is sufficient evidence to support this hypothesis we designed a systematic review of studies on exo-miRNAs in heart diseases causing HF during the last decade. The cardioprotective functions of twenty-four exo-miRNAs derived from bone marrow MSCs (BM-MSCs) are known and the functions of exo-miRNAs from other MSC sources such as adipose tissue, trophoblasts, amniotic fluid, and endometrium were also determined. Inhibition of apoptosis is the most reported biological function and the targets for thirty exo-miRNAs are known. The results from this systematic review support the initial hypothesis and encourage us to test it in future experimental research works but more importantly, we seek to encourage other researchers in the field to propose other hypotheses aimed at the possible use of exo-miRNAs in HF secondary to cardiac disease.

Clinical implications of differential functional capacity between tissue-specific human mesenchymal stromal/stem cells.

Over the past two decades, there has been an explosion in the numbers of clinical trials using mesenchymal stem cells (MSCs). While the safety profile of MSC therapy has been excellent, therapeutic success has not been as robust as expected. In addition to variabilities inherent in all live-cell products because of donor-specific differences and manufacturing practices, MSCs may have an additional layer of complexity due to the availability of many tissues/organ sources for isolation. Since first isolation from the bone marrow (BM) over 50 years ago, human MSCs have been robustly found in multiple tissues/organs. The increased variety of MSC sources is reflected in clinical trials: while BMMSCs was used in nearly all trials prior to 2008, they are used in less than 50% of clinical trials in recent years. While the majority of single-source MSC preclinical data accumulated over the past several decades do reveal biological differences between tissue-specific sources of MSCs, studies directly comparing different MSC sources are relatively rare. In this Review, we summarise these past findings and also specifically focus on studies comparing MSCs isolated from the most commonly utilised sources of BM, adipose tissue and post-partum discarded extraembryonic tissue. The MSC functions discussed here include paraxial mesodermal trilineage differentiation capacity, and also other well-studied and translationally relevant MSC functions of haematopoietic support, immunomodulation and paracrine capacities. Finally, we will discuss the implications of tissue-specific MSC functional differences on future research avenues, manufacturing practices, as well as clinical implementation.

Minimum criteria for defining induced mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are a promising cell type for cell-based therapies. The therapeutic potential of MSCs has been verified in preclinical and clinical studies, however; low cell number in adult tissues, restricted expansion and differentiation capacity, and donor-related heterogeneity limit their use. To address these issues, there has been considerable interest in induced pluripotent stem cells (iPSCs) derived MSCs (induced mesenchymal stem cells [iMSCs]). Investigators obtain iMSCs from iPSCs of different origins, with variable methods of generation and expansion. Results of current studies have suggested iMSCs as a unique alternative source of MSCs. However, iMSCs are defined using the same criteria (proposed previously for primary MSCs by the International Society for Cellular Therapy [ISCT]) without realizing the distinct nature of iMSCs as compared to primary MSCs. To rationally define iMSCs, additional characterization is proposed along with ISCT's minimum criteria for defining primary MSCs. Minimum criteria for defining iMSCs should include (1) spindle-shaped morphology, (2) plastic adherent growth, (3) positive expression of CD29, CD44, CD73, CD90, CD105, along with negative expression of hematopoietic markers (CD45, CD34, CD14 or CD11b, CD79α or CD19, HLA-DR), (4) lack of expression of iPSCs induction factors, (5) trilineage differentiation potential, (6) lack of ability to form teratoma, and (7) release of MSC relevant paracrine factors. Defining the minimum criteria for iMSCs will be of great interest in the field and will provide a uniform description and identification of iMSCs to expedite progress in the field. Furthermore, due to increased interest in the clinical use of iMSCs, the above-mentioned additional characterization before the clinical application is important to avoid unwanted complications for recipients.