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Best Practice & Research. Clinical... Feb 2016The discovery of mesenchymal stem cells (MSCs) in perinatal sources, such as the amniotic fluid (AF) and the umbilical connective tissue, the so-called Wharton's jelly... (Review)
Review
The discovery of mesenchymal stem cells (MSCs) in perinatal sources, such as the amniotic fluid (AF) and the umbilical connective tissue, the so-called Wharton's jelly (WJ), has transformed them into promising stem cell grafts for the application in regenerative medicine. The advantages of AF-MSCs and WJ-MSCs over adult MSCs, such as bone marrow-derived mesenchymal stem cells (BM-MSCs), include their minimally invasive isolation procedure, their more primitive cell character without being tumourigenic, their low immunogenicity and their potential autologous application in congenital disorders and when cryopreserved in adulthood. This chapter gives an overview of the biology of AF-MSCs and WJ-MSCs, and their regenerative potential based on the results of recent preclinical and clinical studies. In the end, open questions concerning the use of WJ-MSCs and AF-MSCs in regenerative medicine will be emphasized.
Topics: Amniotic Fluid; Animals; Brain Diseases; Cell Differentiation; Cell Movement; Diabetes Mellitus; Disease Models, Animal; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Regeneration; Skin; Skin Physiological Phenomena; Wharton Jelly
PubMed: 26482184
DOI: 10.1016/j.bpobgyn.2015.07.006 -
Oxidative Medicine and Cellular... 2017Mesenchymal stem cells (MSCs) are multipotent cells that are currently being investigated in a wide variety of clinical trials for their anti-inflammatory and...
Mesenchymal stem cells (MSCs) are multipotent cells that are currently being investigated in a wide variety of clinical trials for their anti-inflammatory and immunomodulatory properties as well as their osteogenic and chondrogenic capabilities. However, there are considerable interdonor variability and heterogeneity of MSC populations, making it challenging to compare different products. Furthermore, proliferation, differentiation, and immunomodulation of MSCs decrease with aging and ex vivo expansion. The sirtuins have emerged as a class of protein deacylases involved in aging, oxidative stress, and metabolism. Sirtuin 3 (SIRT3) is the major mitochondrial deacetylase involved in reducing oxidative stress while preserving oxidative metabolism, and its levels have been shown to decrease with age. This study investigated the role of SIRT3 in MSC differentiation and aging. As MSCs were expanded ex vivo, SIRT3 levels decreased. In addition, SIRT3 depletion reduced MSC differentiation into adipocytes and osteoblasts. Furthermore, overexpression of SIRT3 in later-passage MSCs reduced aging-related senescence, reduced oxidative stress, and enhanced their ability to differentiate. These data suggest that overexpressing SIRT3 might represent a strategy to increase the quality and quantity of MSCs utilized for clinical applications.
Topics: Cell Differentiation; Cellular Senescence; Humans; Immunophenotyping; Mesenchymal Stem Cells; Sirtuin 3
PubMed: 28717408
DOI: 10.1155/2017/5841716 -
Transfusion and Apheresis Science :... Feb 2021Mesenchymal stromal cells (MSC) are multipotent precursor cells that can be derived from a variety of tissue sources, with a working definition based on... (Review)
Review
Mesenchymal stromal cells (MSC) are multipotent precursor cells that can be derived from a variety of tissue sources, with a working definition based on immunophenotyping and cell differentiation capacity. Despite historical roots in the field of tissue engineering, they have generated great interest as cell therapies for their immune regulatory function, which has led to numerous clinical trials for a range of inflammatory and autoimmune conditions. Importantly, due to the lack of traditional MHC expression and their expression of other immune regulatory proteins, they can be used from third party donors without generating a dangerous alloreactivity. After 20 years of clinical trials, they have earned themselves an excellent safety record but are currently only approved for use in Canada, New Zealand, Japan, South Korea and Europe due to a lack of consistent efficacy data. In the United States, the indication that has seen the most progress is steroid refractory acute graft-versus-host disease (SR-aGVHD). Issues with early clinical trials can be attributed to both challenges with defining optimal patient populations and trial design as well as limitations related to commercial manufacturing. Earlier this year, the encouraging data for a repeat Phase III trial in pediatric patients with SR-aGVHD was published. This review provides information on the proposed mechanism of action of MSCs, clinical utilization of MSCs with focus on SR-aGVHD and potential modalities that can improve the efficacy of MSCs.
Topics: Female; Humans; Male; Mesenchymal Stem Cells
PubMed: 33495081
DOI: 10.1016/j.transci.2021.103058 -
Tissue & Cell Jun 2020Mesenchymal stem cells (MSCs) are multipotent, genomic stable, self-renewable, and culturally expandable adult stem cells. MSCs facilitate tissue development,... (Review)
Review
BACKGROUND
Mesenchymal stem cells (MSCs) are multipotent, genomic stable, self-renewable, and culturally expandable adult stem cells. MSCs facilitate tissue development, maintenance and repair, and produce secretory factors that support engraftment and trophic functions, marking them an attractive option in cell therapy, regenerative medicine and tissue engineering.
METHOD
In this review, we summarize the recent researches regarding the isolation and characterization of MSCs, therapeutic applications and advanced engineering techniques. We also discuss the advantages and limitations that remain to be overcome for MSCs based therapy.
RESULTS
It has been demonstrated that MSCs are able to modulate endogenous tissue and immune cells. Preclinical studies and early phase clinical trials have shown their great potential for tissue engineering of bone, cartilage, marrow stroma, muscle, fat, and other connective tissues.
CONCLUSIONS
MSC-based therapy show considerable promise to rebuild damaged or diseased tissues, which could be a promising therapeutic method for regeneration medicine.
Topics: Adult Stem Cells; Bone and Bones; Cardiovascular Abnormalities; Cell Differentiation; Humans; Inflammation; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Regenerative Medicine; Tissue Engineering
PubMed: 32473704
DOI: 10.1016/j.tice.2020.101330 -
Stem Cell Reviews and Reports Apr 2018Mesenchymal stem cells (MSCs) are promising resource for the therapy of inflammatory bowel diseases (IBDs) on the grounds of their differentiation capabilities and... (Review)
Review
Mesenchymal stem cells (MSCs) are promising resource for the therapy of inflammatory bowel diseases (IBDs) on the grounds of their differentiation capabilities and immuno-modulatory characteristics. Results of clinical studies indicate that local application of MSCs is a secure and beneficial approach for the treatment of perianal fistulas while systemic application of MSCs leads to the attenuation or aggravation of IBDs. Herein, we emphasized molecular mechanisms and approaches that should improve efficacy of MSC-based therapy of IBDs.
Topics: Animals; Cell- and Tissue-Based Therapy; Humans; Inflammatory Bowel Diseases; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 29177796
DOI: 10.1007/s12015-017-9789-2 -
Laboratory Investigation; a Journal of... Oct 2017Obesity is now a major public health problem worldwide. Lifestyle modification to reduce the characteristic excess body adiposity is important in the treatment of... (Review)
Review
Obesity is now a major public health problem worldwide. Lifestyle modification to reduce the characteristic excess body adiposity is important in the treatment of obesity, but effective therapeutic intervention is still needed to control what has become an obesity epidemic. Unfortunately, many anti-obesity drugs have been withdrawn from market due to adverse side effects. Bariatric surgery therefore remains the most effective therapy for severe cases, although such surgery is invasive and researchers continue to seek new control strategies for obesity. Mesenchymal stem cells (MSCs) are a major source of adipocyte generation, and studies have been conducted into the potential roles of MSCs in treating obesity. However, despite significant progress in stem cell research and its potential applications for obesity, adipogenesis is a highly complex process and the molecular mechanisms governing MSC adipogenesis remain ill defined. In particular, successful clinical application of MSCs will require extensive identification and characterization of the transcriptional regulators controlling MSC adipogenesis. Since obesity is associated with the incidence of multiple important comorbidities, an in-depth understanding of the relationship between MSC adipogenesis and the comorbidities of obesity is also necessary to evaluate the potential of effective and safe MSC-based therapies for obesity. In addition, brown adipogenesis is an attractive topic from the viewpoint of therapeutic innovation and future research into MSC-based brown adipogenesis could lead to a novel breakthrough. Ongoing stem cell studies and emerging research fields such as epigenetics are expected to elucidate the complicated mechanisms at play in MSC adipogenesis and develop novel MSC-based therapeutic options for obesity. This review discusses the current understanding of MSCs in adipogenesis and their potential clinical applications for obesity.
Topics: Adipogenesis; Animals; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Obesity; Translational Research, Biomedical
PubMed: 28414326
DOI: 10.1038/labinvest.2017.42 -
Advances in Experimental Medicine and... 2018Stem cells have the ability to perpetuate themselves through self-renewal and generate mature cells of a particular tissue through differentiation. Mesenchymal stem... (Review)
Review
Stem cells have the ability to perpetuate themselves through self-renewal and generate mature cells of a particular tissue through differentiation. Mesenchymal stem cells (MSCs) play an important role in tissue homeostasis - supporting tissue regeneration. MSCs are rare pluripotent cells supporting hematopoietic and mesenchymal cell lineages. MSCs have a great therapeutic potential in cancer therapy, as well as stem cell exosome and/or microvesicle-mediated tissue regeneration. In this review, the use of hMSCs in stem cell-mediated cancer therapy is discussed.
Topics: Cell Differentiation; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Neoplasms
PubMed: 28730382
DOI: 10.1007/5584_2017_64 -
International Journal of Molecular... Aug 2014Mesenchymal stem cells (MSCs) are multipotent stem cells that give rise to various cell types of the mesodermal germ layer. Because of their unique ability to home in on... (Review)
Review
Mesenchymal stem cells (MSCs) are multipotent stem cells that give rise to various cell types of the mesodermal germ layer. Because of their unique ability to home in on injured and cancerous tissues, MSCs are of great potential in regenerative medicine. MSCs also contribute to reparative processes in different pathological conditions, including cardiovascular diseases and cancer. However, many studies have shown that only a small proportion of transplanted MSCs can actually survive and be incorporated into host tissues. The effects of MSCs cannot be fully explained by their number. Recent discoveries suggest that microparticles (MPs) derived from MSCs may be important for the physiological functions of their parent. Though the physiological role of MSC-MPs is currently not well understood, inspiring results indicate that, in tissue repair and anti-cancer therapy, MSC-MPs have similar pro-regenerative and protective properties as their cellular counterparts. Thus, MSC-MPs represent a promising approach that may overcome the obstacles and risks associated with the use of native or engineered MSCs.
Topics: Cell-Derived Microparticles; Humans; Mesenchymal Stem Cells
PubMed: 25196436
DOI: 10.3390/ijms150814348 -
Artificial Cells, Nanomedicine, and... 2016Mesenchymal stem cells (MSCs) are non-hematopoietic, multipotent progenitor cells which reside in bone marrow (BM), support homing of hematopoietic stem cells (HSCs) and... (Review)
Review
Mesenchymal stem cells (MSCs) are non-hematopoietic, multipotent progenitor cells which reside in bone marrow (BM), support homing of hematopoietic stem cells (HSCs) and self-renewal in the BM. These cells have the potential to differentiate into tissues of mesenchymal origin, such as fibroblasts, adipocytes, cardiomyocytes, and stromal cells. MSCs can express surface molecules like CD13, CD29, CD44, CD73, CD90, CD166, CXCL12 and toll-like receptors (TLRs). Different factors, such as TGF-β, IL-10, IDO, PGE-2, sHLA-G5, HO, and Galectin-3, secreted by MSCs, induce interaction in cell to cell immunomodulatory effects on innate and adaptive cells of the immune system. Furthermore, these cells can stimulate and increase the TH2 and regulatory T-cells through inhibitory effects on the immune system. MSCs originate from the BM and other tissues including the brain, adipose tissue, peripheral blood, cornea, thymus, spleen, fallopian tube, placenta, Wharton's jelly and umbilical cord blood. Many studies have focused on two significant features of MSC therapy: (I) MSCs can modulate T-cell-mediated immunological responses, and (II) systemically administered MSCs home in to sites of ischemia or injury. In this review, we describe the known mechanisms of immunomodulation and homing of MSCs. As a result, this review emphasizes the functional role of MSCs in modulating immune responses, their capability in homing to injured tissue, and their clinical therapeutic potential.
Topics: Adaptive Immunity; Animals; Biotechnology; Cell- and Tissue-Based Therapy; Humans; Immunity, Innate; Immunomodulation; Mesenchymal Stem Cells
PubMed: 25340260
DOI: 10.3109/21691401.2014.968823 -
Stem Cells (Dayton, Ohio) Jan 2024Mesenchymal stem cells (MSCs) are widely used in therapy, but the differences between MSCs of various origins and their ability to undergo osteogenic differentiation and...
Mesenchymal stem cells (MSCs) are widely used in therapy, but the differences between MSCs of various origins and their ability to undergo osteogenic differentiation and produce extracellular matrix are not fully understood. To address this, we conducted a comparative analysis of mesenchymal cell primary cultures from 6 human sources, including osteoblast-like cells from the adult femur, adipose-derived stem cells, Wharton's jelly-derived mesenchymal cells, gingival fibroblasts, dental pulp stem cells, and periodontal ligament stem cells. We analyzed these cells' secretome, proteome, and transcriptome under standard and osteogenic cultivation conditions. Despite the overall similarity in osteogenic differentiation, the cells maintain their embryonic specificity after isolation and differentiation in vitro. Furthermore, we propose classifying mesenchymal cells into 3 groups: dental stem cells of neural crest origin, mesenchymal stem cells, and fetal stem cells. Specifically, fetal stem cells have the most promising secretome for various applications, while mesenchymal stem cells have a specialized secretome optimal for extracellular matrix production. Nevertheless, mesenchymal cells from all sources secreted core bone extracellular matrix-associated proteins. In conclusion, our study illuminates the distinctive characteristics of mesenchymal stem cells from various sources, providing insights into their potential applications in regenerative medicine and enhancing our understanding of the inherent diversity of mesenchymal cells in vivo.
Topics: Adult; Humans; Osteogenesis; Wharton Jelly; Cell Differentiation; Cell Culture Techniques; Cells, Cultured; Mesenchymal Stem Cells
PubMed: 37931142
DOI: 10.1093/stmcls/sxad081