scholarly journals Therapeutic Potential of Mesenchymal Stem Cells in Regenerative Medicine

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Devang M. Patel ◽  
Jainy Shah ◽  
Anand S. Srivastava
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Tissue Repair ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Genetic Disorders ◽  
Repair Process ◽  
Attractive Candidate

Mesenchymal stem cells (MSCs) are stromal cells that have the ability to self-renew and also exhibit multilineage differentiation into both mesenchymal and nonmesenchymal lineages. The intrinsic properties of these cells make them an attractive candidate for clinical applications. MSCs are of keen interest because they can be isolated from a small aspirate of bone marrow or adipose tissues and can be easily expandedin vitro. Moreover, their ability to modulate immune responses makes them an even more attractive candidate for regenerative medicine as allogeneic transplant of these cells is feasible without a substantial risk of immune rejection. MSCs secrete various immunomodulatory molecules which provide a regenerative microenvironment for a variety of injured tissues or organ to limit the damage and to increase self-regulated tissue regeneration. Autologous/allogeneic MSCs delivered via the bloodstream augment the titers of MSCs that are drawn to sites of tissue injury and can accelerate the tissue repair process. MSCs are currently being tested for their potential use in cell and gene therapy for a number of human debilitating diseases and genetic disorders. This paper summarizes the current clinical and nonclinical data for the use of MSCs in tissue repair and potential therapeutic role in various diseases.

scholarly journals Dental Pulp-Derived Mesenchymal Stem Cells for Modeling Genetic Disorders

2021 ◽  
Vol 22 (5) ◽  
pp. 2269
Author(s):  
Keiji Masuda ◽  
Xu Han ◽  
Hiroki Kato ◽  
Hiroshi Sato ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dental Pulp ◽  
Genetic Disorders ◽  
In Vitro Models ◽  
High Plasticity ◽  
Human Teeth ◽  
Clinical Diagnoses ◽  
Models Of Disease

A subpopulation of mesenchymal stem cells, developmentally derived from multipotent neural crest cells that form multiple facial tissues, resides within the dental pulp of human teeth. These stem cells show high proliferative capacity in vitro and are multipotent, including adipogenic, myogenic, osteogenic, chondrogenic, and neurogenic potential. Teeth containing viable cells are harvested via minimally invasive procedures, based on various clinical diagnoses, but then usually discarded as medical waste, indicating the relatively low ethical considerations to reuse these cells for medical applications. Previous studies have demonstrated that stem cells derived from healthy subjects are an excellent source for cell-based medicine, tissue regeneration, and bioengineering. Furthermore, stem cells donated by patients affected by genetic disorders can serve as in vitro models of disease-specific genetic variants, indicating additional applications of these stem cells with high plasticity. This review discusses the benefits, limitations, and perspectives of patient-derived dental pulp stem cells as alternatives that may complement other excellent, yet incomplete stem cell models, such as induced pluripotent stem cells, together with our recent data.

scholarly journals Adropin-based dual treatment enhances the therapeutic potential of mesenchymal stem cells in rat myocardial infarction

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
HuiYa Li ◽  
DanQing Hu ◽  
Guilin Chen ◽  
DeDong Zheng ◽  
ShuMei Li ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Paracrine Factors ◽  
Dual Treatment

AbstractBoth weak survival ability of stem cells and hostile microenvironment are dual dilemma for cell therapy. Adropin, a bioactive substance, has been demonstrated to be cytoprotective. We therefore hypothesized that adropin may produce dual protective effects on the therapeutic potential of stem cells in myocardial infarction by employing an adropin-based dual treatment of promoting stem cell survival in vitro and modifying microenvironment in vivo. In the current study, adropin (25 ng/ml) in vitro reduced hydrogen peroxide-induced apoptosis in rat bone marrow mesenchymal stem cells (MSCs) and improved MSCs survival with increased phosphorylation of Akt and extracellular regulated protein kinases (ERK) l/2. Adropin-induced cytoprotection was blocked by the inhibitors of Akt and ERK1/2. The left main coronary artery of rats was ligated for 3 or 28 days to induce myocardial infarction. Bromodeoxyuridine (BrdU)-labeled MSCs, which were in vitro pretreated with adropin, were in vivo intramyocardially injected after ischemia, following an intravenous injection of 0.2 mg/kg adropin (dual treatment). Compared with MSCs transplantation alone, the dual treatment with adropin reported a higher level of interleukin-10, a lower level of tumor necrosis factor-α and interleukin-1β in plasma at day 3, and higher left ventricular ejection fraction and expression of paracrine factors at day 28, with less myocardial fibrosis and higher capillary density, and produced more surviving BrdU-positive cells at day 3 and 28. In conclusion, our data evidence that adropin-based dual treatment may enhance the therapeutic potential of MSCs to repair myocardium through paracrine mechanism via the pro-survival pathways.

scholarly journals Improved healing of critical-size femoral defect in osteoporosis rat models using 3D elastin/polycaprolactone/nHA scaffold in combination with mesenchymal stem cells

2021 ◽  
Vol 32 (3) ◽  
Author(s):  
Fatemeh Hejazi ◽  
Vahid Ebrahimi ◽  
Mehrdad Asgary ◽  
Abbas Piryaei ◽  
Mohammad Javad Fridoni ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Healing ◽  
Critical Size ◽  
Therapeutic Potential ◽  
Rna Extraction ◽  
Osteotomy Site ◽  
Cell Groups ◽  
The Right

AbstractOsteoporosis is a common bone disease that results in elevated risk of fracture, and delayed bone healing and impaired bone regeneration are implicated by this disease. In this study, Elastin/Polycaprolactone/nHA nanofibrous scaffold in combination with mesenchymal stem cells were used to regenerate bone defects. Cytotoxicity, cytocompatibility and cellular morphology were evaluated in vitro and observations revealed that an appropriate environment for cellular attachment, growth, migration, and proliferation is provided by this scaffold. At 3 months following ovariectomy (OVX), the rats were used as animal models with an induced critical size defect in the femur to evaluate the therapeutic potential of osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) seeded on 3 dimension (3D) scaffolds. In this experimental study, 24 female Wistar rats were equally divided into three groups: Control, scaffold (non-seeded BM-MSC), and scaffold + cell (seeded BM-MSC) groups. 30 days after surgery, the right femur was removed, and underwent a stereological analysis and RNA extraction in order to examine the expression of Bmp-2 and Vegf genes. The results showed a significant increase in stereological parameters and expression of Bmp-2 and Vegf in scaffold and scaffold + cell groups compared to the control rats. The present study suggests that the use of the 3D Elastin/Polycaprolactone (PCL)/Nano hydroxyapatite (nHA) scaffold in combination with MSCs may improve the fracture regeneration and accelerates bone healing at the osteotomy site in rats.

Therapeutic Potential of Adipose-Derived Mesenchymal Stem Cells (Admscs) and/or Taurine in Aluminum Chloride-Induced Alzheimer's Disease Rat Model

2021 ◽  
Author(s):  
Mohamed Hosney ◽  
Alaa Sakraan ◽  
Aman Asaad ◽  
Mervat El-Deftar ◽  
Emad Elzayat
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Cell Activation ◽  
Therapeutic Potential ◽  
Brain Homogenate ◽  
Oxidative Stress Marker

Abstract Alzheimer's disease (AD) is the most prevalent type of dementia characterized by its progression, neurobehavioral and neuro-pathological characteristics, leading to a diverse neuronal loss. Adipose-derived mesenchymal stem cells (ADMSCs) have previously proved potential role in preventing the pathogenesis of several neurodegenerative disorders, so regarded as a promising new approach for AD regenerative therapy. Taurine was found to enhance stem cell activation and propagation yielding a higher concentration of neural progenitors and stem cells, and aid to lessen the number of activated microglia leading to down-regulated inflammation in vitro. The present study aimed to investigate the possible therapeutic potential of ADMSCs and/or taurine in treating AD rat model. It was planned to include three successive phases; induction, withdrawal, and therapeutic phases. Fifty male Wistar rats were divided into 2 main groups: control (C) group and AD model group. Behavioral changes, as manifested by the T-Maze experiment, had been recorded. β-amyloid levels had been measured in brain homogenate and serum by ELISA. Oxidative stress marker (MDA), and anti-oxidant enzymes activity (SOD, GSH, and CAT) in brain, as well as serum acetylcholine esterase activity were spectrophotometrically determined. Pro-apoptotic (p53 and Bax) and anti-apoptotic (Bcl2) gene expression in brain were evaluated using RT-qPCR. The histopathological alterations in brain tissues were also observed. The present study proved the potential therapeutic ability of ADMSCs and/or taurine in alleviating the adverse pathological changes induced by AlCl3 in AD rat model at both physiological and molecular levels.

scholarly journals Current Status of Human Adipose–Derived Stem Cells: Differentiation into Hepatocyte-Like Cells

2011 ◽  
Vol 11 ◽  
pp. 1568-1581 ◽  
Author(s):  
Feras Al Battah ◽  
Joery De Kock ◽  
Tamara Vanhaecke ◽  
Vera Rogiers
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Study Drug ◽  
Current Status ◽  
Human Organ ◽  
Beneficial Effects ◽  
Stems Cells

The shortage of human organ donors and the low cell quality of available liver tissues represent major obstacles for the clinical application of orthotropic liver transplantation and hepatocyte transplantation, respectively. Therefore, worldwide research groups are investigating alternative extrahepatic cell sources. Recentin vitrostudies have demonstrated that mesenchymal stem cells (MSCs) from various sources, including human bone marrow, adipose tissue, and umbilical cord, can be differentiated into hepatocyte-like cells when appropriate conditions are used. In particular, interest exists for human adipose–derived stems cells (hASCs) as an attractive cell source for generating hepatocyte-like cells. The hASCs are multipotent MSCs that reside in adipose tissue, with the ability to self-renew and differentiate into multiple cell lineages. Moreover, these cells can secrete multiple growth factors and cytokines that exert beneficial effects on organ or tissue injury. In this review, we will not only present recent data regarding hASC biology, their isolation, and differentiation capability towards hepatocytes, but also the potential application of hASC-derived hepatocytes to study drug toxicity. Additionally, this review will discuss the therapeutic potential of hASCs as undifferentiated cells in liver regeneration.

scholarly journals The Role of Paracrine Regulation of Mesenchymal Stem Cells in the Crosstalk With Macrophages in Musculoskeletal Diseases: A Systematic Review

2020 ◽  
Vol 8 ◽  
Author(s):  
Hongtao Xu ◽  
Chien-Wei Lee ◽  
Yu-Fan Wang ◽  
Shuting Huang ◽  
Lih-Ying Shin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Proinflammatory Cytokines ◽  
Therapeutic Potential ◽  
Musculoskeletal Diseases ◽  
Repair Process ◽  
Phenotypic Change ◽  
Phenotypic Alteration ◽  
Mesh Terms ◽  
Novel Approach

The phenotypic change of macrophages (Mφs) plays a crucial role in the musculoskeletal homeostasis and repair process. Although mesenchymal stem cells (MSCs) have been shown as a novel approach in tissue regeneration, the therapeutic potential of MSCs mediated by the interaction between MSC-derived paracrine mediators and Mφs remains elusive. This review focused on the elucidation of paracrine crosstalk between MSCs and Mφs during musculoskeletal diseases and injury. The search method was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane Guidelines. The search strategies included MeSH terms and other related terms of MSC-derived mediators and Mφs. Ten studies formed the basis of this review. The current finding suggested that MSC administration promoted proliferation and activation of CD163+ or CD206+ M2 Mφs in parallel with reduction of proinflammatory cytokines and increase in anti-inflammatory cytokines. During such period, Mφs also induced MSCs into a motile and active phenotype via the influence of proinflammatory cytokines. Such crosstalk between Mφs and MSCs further strengthens the effect of paracrine mediators from MSCs to regulate Mφs phenotypic alteration. In conclusion, MSCs in musculoskeletal system, mediated by the interaction between MSC paracrine and Mφs, have therapeutic potential in musculoskeletal diseases.

scholarly journals Optimal H2O2 preconditioning to improve bone marrow mesenchymal stem cells’ engraftment in wound healing

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ling Guo ◽  
Juan Du ◽  
Dan-feng Yuan ◽  
Ya Zhang ◽  
Shu Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Optimal Protocol ◽  
Marrow Mesenchymal Stem Cells ◽  
Gsk 3Β ◽  
Migration Capacity

Abstract Background The transplantation of bone marrow mesenchymal stem cells (BMSCs) is a promising therapeutic strategy for wound healing. However, the poor migration capacity and low survival rate of transplanted BMSCs in wounds weaken their potential application. Objective To identify the optimal protocol for BMSCs preconditioned with H2O2 and improve the therapeutic efficacy using H2O2-preconditioned BMSCs in wound healing. Methods Mouse BMSCs were exposed to various concentrations of H2O2, and the key cellular functional properties were assessed to determine the optimal precondition with H2O2. The H2O2-preconditioned BMSCs were transplanted into mice with full-thickness excisional wounds to evaluate their healing capacity and tissue engraftment. Results Treatment BMSCs with 50 μM H2O2 for 12 h could significantly enhance their proliferation, migration, and survival by maximizing the upregulation of cyclin D1, SDF-1, and its receptors CXCR4/7 expressions, and activating the PI3K/Akt/mTOR pathway, but inhibiting the expression of p16 and GSK-3β. Meanwhile, oxidative stress-induced BMSC apoptosis was also significantly attenuated by the same protocol pretreatment with a decreased ratio of Bax/Bcl-2 and cleaved caspase-9/3 expression. Moreover, after the identification of the optimal protocol of H2O2 precondition in vitro, the migration and tissue engraftment of transfused BMSCs with H2O2 preconditioning were dramatically increased into the wound site as compared to the un-preconditioned BMSCs. The increased microvessel density and the speedy closure of the wounds were observed after the transfusion of H2O2-preconditioned BMSCs. Conclusions The findings suggested that 50 μM H2O2 pretreated for 12 h is the optimal precondition for the transplantation of BMSCs, which gives a considerable insight that this protocol may be served as a promising candidate for improving the therapeutic potential of BMSCs for wound healing.

scholarly journals A Simplified Method for the Aspiration of Bone Marrow from Patients Undergoing Hip and Knee Joint Replacement for Isolating Mesenchymal Stem Cells and In Vitro Chondrogenesis

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Subhash C. Juneja ◽  
Sowmya Viswanathan ◽  
Milan Ganguly ◽  
Christian Veillette
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Isolation And Characterization ◽  
Standard Operating ◽  
Total Knee ◽  
Detailed Protocol

The procedure for aspiration of bone marrow from the femur of patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA) may vary from an OR (operating room) to OR based on the surgeon’s skill and may lead to varied extent of clotting of the marrow and this, in turn, presents difficulty in the isolation of mesenchymal stem cells (MSCs) from such clotted bone marrow. We present a simple detailed protocol for aspirating bone marrow from such patients, isolation, and characterization of MSCs from the aspirated bone marrow specimens and show that the bone marrow presented no clotting or exhibited minimal clotting. This represents an economical source and convenient source of MSCs from bone marrow for use in regenerative medicine. Also, we presented the detailed protocol and showed that the MSCs derived from such bone marrow specimens exhibited MSCs characteristics and generated micromass cartilages, the recipe for regenerative medicine for osteoarthritis. The protocols we presented can be used as standard operating procedures (SOPs) by researchers and clinicians.

scholarly journals Safety of Mesenchymal Stem Cells for Clinical Application

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Youwei Wang ◽  
Zhi-bo Han ◽  
Yong-ping Song ◽  
Zhong Chao Han
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Therapeutic Agents ◽  
Great Promise ◽  
Safety Issues ◽  
Human Use

Mesenchymal stem cells (MSCs) hold great promise as therapeutic agents in regenerative medicine and autoimmune diseases, based on their differentiation abilities and immunosuppressive properties. However, the therapeutic applications raise a series of questions about the safety of culture-expanded MSCs for human use. This paper summarized recent findings about safety issues of MSCs, in particular their genetic stability in long-termin vitroexpansion, their cryopreservation, banking, and the role of serum in the preparation of MSCs.

scholarly journals Curcumin Alleviates the Senescence of Canine Bone Marrow Mesenchymal Stem Cells during In Vitro Expansion by Activating the Autophagy Pathway

2021 ◽  
Vol 22 (21) ◽  
pp. 11356
Author(s):  
Jiaqiang Deng ◽  
Ping Ouyang ◽  
Weiyao Li ◽  
Lijun Zhong ◽  
Congwei Gu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Mrna Expression ◽  
Light Chain ◽  
Therapeutic Potential ◽  
Cell Model ◽  
Biological Aging ◽  
Aging Effects

Senescence in mesenchymal stem cells (MSCs) not only hinders the application of MSCs in regenerative medicine but is also closely correlated with biological aging and the development of degenerative diseases. In this study, we investigated the anti-aging effects of curcumin (Cur) on canine bone marrow-derived MSCs (cBMSCs), and further elucidated the potential mechanism of action based on the modulation of autophagy. cBMSCs were expanded in vitro with standard procedures to construct a cell model of premature senescence. Our evidence indicates that compared with the third passage of cBMSCs, many typical senescence-associated phenotypes were observed in the sixth passage of cBMSCs. Cur treatment can improve cBMSC survival and retard cBMSC senescence according to observations that Cur (1 μM) treatment can improve the colony-forming unit-fibroblasts (CFU-Fs) efficiency and upregulated the mRNA expression of pluripotent transcription factors (SOX-2 and Nanog), as well as inhibiting the senescence-associated beta-galactosidase (SA-β-gal) activities and mRNA expression of the senescence-related markers (p16 and p21) and pro-inflammatory molecules (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)). Furthermore, Cur (0.1 μM~10 μM) was observed to increase autophagic activity, as identified by upregulation of microtubule-associated protein 1 light chain 3 (LC3), unc51-like autophagy-activating kinase-1 (ULK1), autophagy-related gene (Atg) 7 and Atg12, and the generation of type II of light chain 3 (LC3-II), thereby increasing autophagic vacuoles and acidic vesicular organelles, as well as causing a significant decrease in the p62 protein level. Moreover, the autophagy activator rapamycin (RAP) and Cur were found to partially ameliorate the senescent features of cBMSCs, while the autophagy inhibitor 3-methyladenine (3-MA) was shown to aggravate cBMSCs senescence and Cur treatment was able to restore the suppressed autophagy and counteract 3-MA-induced cBMSC senescence. Hence, our study highlights the important role of Cur-induced autophagy and its effects for ameliorating cBMSC senescence and provides new insight for delaying senescence and improving the therapeutic potential of MSCs.

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