The therapeutic potential of mesenchymal stem cells in treating osteoporosis

AbstractOsteoporosis (OP), a common systemic metabolic bone disease, is characterized by low bone mass, increasing bone fragility and a high risk of fracture. At present, the clinical treatment of OP mainly involves anti-bone resorption drugs and anabolic agents for bone, but their long-term use can cause serious side effects. The development of stem cell therapy and regenerative medicine has provided a new approach to the clinical treatment of various diseases, even with a hope for cure. Recently, the therapeutic advantages of the therapy have been shown for a variety of orthopedic diseases. However, these stem cell-based researches are currently limited to animal models; the uncertainty regarding the post-transplantation fate of stem cells and their safety in recipients has largely restricted the development of human clinical trials. Nevertheless, the feasibility of mesenchymal stem cells to treat osteoporotic mice has drawn a growing amount of intriguing attention from clinicians to its potential of applying the stem cell-based therapy as a new therapeutic approach to OP in the future clinic. In the current review, therefore, we explored the potential use of mesenchymal stem cells in human OP treatment.

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Cell-Based Therapy for Stroke

Stroke ◽

10.1161/strokeaha.120.030618 ◽

2020 ◽

Vol 51 (9) ◽

pp. 2854-2862 ◽

Cited By ~ 1

Author(s):

You Jeong Park ◽

Kuniyasu Niizuma ◽

Maxim Mokin ◽

Mari Dezawa ◽

Cesar V. Borlongan

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Ischemic Stroke ◽

Cell Therapy ◽

Therapeutic Potential ◽

Host Tissue ◽

In Vivo Models ◽

Cell Based Therapy ◽

Muse Cells

Stem cell-based regenerative therapies may rescue the central nervous system following ischemic stroke. Mesenchymal stem cells exhibit promising regenerative capacity in in vitro studies but display little to no incorporation in host tissue after transplantation in in vivo models of stroke. Despite these limitations, clinical trials using mesenchymal stem cells have produced some functional benefits ascribed to their ability to modulate the host’s inflammatory response coupled with their robust safety profile. Regeneration of ischemic brain tissue using stem cells, however, remains elusive in humans. Multilineage-differentiating stress-enduring (Muse) cells are a distinct subset of mesenchymal stem cells found sporadically in connective tissue of nearly every organ. Since their discovery in 2010, these endogenous reparative stem cells have been investigated for their therapeutic potential against a variety of diseases, including acute myocardial infarction, stroke, chronic kidney disease, and liver disease. Preclinical studies have exemplified Muse cells’ unique ability mobilize, differentiate, and engraft into damaged host tissue. Intravenously transplanted Muse cells in mouse lacunar stroke models afforded functional recovery and long-term engraftment into the host neural network. This mini-review article highlights these biological properties that make Muse cells an exceptional candidate donor source for cell therapy in ischemic stroke. Elucidating the mechanism behind the therapeutic potential of Muse cells will undoubtedly help optimize stem cell therapy for stroke and advance the field of regenerative medicine.

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The Therapeutic Potential of Inflamed Gingiva-Derived Mesenchymal Stem Cells in Preclinical Studies: A Scoping Review of a Unique Biomedical Waste

Stem Cells International ◽

10.1155/2021/6619170 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Gamilah Al-Qadhi ◽

Sarah Al-Rai ◽

Layla Hafed

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Scoping Review ◽

Therapeutic Potential ◽

Fiber Formation ◽

Current Evidence ◽

Preclinical Studies ◽

Cell Based Therapy ◽

Scoping Reviews

Searching for considerable abundance, simple, and accessible sources in stem cell-based therapy opens the door for isolation of a new population of oral/dental stem cells known as inflamed gingiva-derived mesenchymal stem cells, which have recently come to light with promising therapeutic potential in tissue regenerative therapy. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines, this scoping review is aimed at highlighting the possible therapeutic potential of inflamed gingiva-derived mesenchymal stem cells in preclinical studies carried out to date and presenting the current evidence depends upon their comparison to the healthy gingiva-derived mesenchymal stem cells or other mesenchymal stem cell sources. A comprehensive electronic search using (PubMed, Embase, Scopus, and Web of Science) databases and a manual search of relevant references were conducted until June 2020. Included studies were assessed using a combination tool, including the guidelines for reporting preclinical in vitro studies on dental materials, which were based on the modification of the Consolidated Standards of Reporting Trial checklist and the guidelines for animal research: reporting of in vivo experiments. The initial research provided 360 articles, with 13 articles that met the inclusion criteria. While most of the included studies lacked randomization, blinding, and sample size calculation, they were designed accurately in other aspects of the guidelines. The results of this scoping review indicated that inflamed gingiva-derived mesenchymal stem cells could be effective in terms of osteogenic differentiation, collagen fiber formation, immunoregulation, migration capacity, and testing of dental material and may present a reliable alternative source for healthy gingiva-derived mesenchymal stem cells.

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Therapeutic Potential of Amniotic Fluid Derived Mesenchymal Stem Cells Based on their Differentiation Capacity and Immunomodulatory Properties

Current Stem Cell Research & Therapy ◽

10.2174/1574888x14666190222201749 ◽

2019 ◽

Vol 14 (4) ◽

pp. 327-336 ◽

Cited By ~ 9

Author(s):

Carl R. Harrell ◽

Marina Gazdic ◽

Crissy Fellabaum ◽

Nemanja Jovicic ◽

Valentin Djonov ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Animal Models ◽

Amniotic Fluid ◽

Therapeutic Potential ◽

Inflammatory Diseases ◽

Therapeutic Effects ◽

Differentiation Potential ◽

Differentiation Capacity ◽

Cell Based Therapy

Background: Amniotic Fluid Derived Mesenchymal Stem Cells (AF-MSCs) are adult, fibroblast- like, self-renewable, multipotent stem cells. During the last decade, the therapeutic potential of AF-MSCs, based on their huge differentiation capacity and immunomodulatory characteristics, has been extensively explored in animal models of degenerative and inflammatory diseases. Objective: In order to describe molecular mechanisms responsible for the therapeutic effects of AFMSCs, we summarized current knowledge about phenotype, differentiation potential and immunosuppressive properties of AF-MSCs. Methods: An extensive literature review was carried out in March 2018 across several databases (MEDLINE, EMBASE, Google Scholar), from 1990 to present. Keywords used in the selection were: “amniotic fluid derived mesenchymal stem cells”, “cell-therapy”, “degenerative diseases”, “inflammatory diseases”, “regeneration”, “immunosuppression”. Studies that emphasized molecular and cellular mechanisms responsible for AF-MSC-based therapy were analyzed in this review. Results: AF-MSCs have huge differentiation and immunosuppressive potential. AF-MSCs are capable of generating cells of mesodermal origin (chondrocytes, osteocytes and adipocytes), neural cells, hepatocytes, alveolar epithelial cells, insulin-producing cells, cardiomyocytes and germ cells. AF-MSCs, in juxtacrine or paracrine manner, regulate proliferation, activation and effector function of immune cells. Due to their huge differentiation capacity and immunosuppressive characteristic, transplantation of AFMSCs showed beneficent effects in animal models of degenerative and inflammatory diseases of nervous, respiratory, urogenital, cardiovascular and gastrointestinal system. Conclusion: Considering the fact that amniotic fluid is obtained through routine prenatal diagnosis, with minimal invasive procedure and without ethical concerns, AF-MSCs represents a valuable source for cell-based therapy of organ-specific or systemic degenerative and inflammatory diseases.

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Mesenchymal Stem Cell-Derived Exosomes: Biological Function and Their Therapeutic Potential in Radiation Damage

Cells ◽

10.3390/cells10010042 ◽

2020 ◽

Vol 10 (1) ◽

pp. 42

Author(s):

Xiaoyu Pu ◽

Siyang Ma ◽

Yan Gao ◽

Tiankai Xu ◽

Pengyu Chang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Radiation Damage ◽

Therapeutic Potential ◽

Damage Model ◽

Bioactive Substances ◽

Radiation Induced ◽

Insight Into

Radiation-induced damage is a common occurrence in cancer patients who undergo radiotherapy. In this setting, radiation-induced damage can be refractory because the regeneration responses of injured tissues or organs are not well stimulated. Mesenchymal stem cells have become ideal candidates for managing radiation-induced damage. Moreover, accumulating evidence suggests that exosomes derived from mesenchymal stem cells have a similar effect on repairing tissue damage mainly because these exosomes carry various bioactive substances, such as miRNAs, proteins and lipids, which can affect immunomodulation, angiogenesis, and cell survival and proliferation. Although the mechanisms by which mesenchymal stem cell-derived exosomes repair radiation damage have not been fully elucidated, we intend to translate their biological features into a radiation damage model and aim to provide new insight into the management of radiation damage.

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Label-Free Rapid Separation and Enrichment of Bone Marrow-Derived Mesenchymal Stem Cells from a Heterogeneous Cell Mixture Using a Dielectrophoresis Device

Sensors ◽

10.3390/s18093007 ◽

2018 ◽

Vol 18 (9) ◽

pp. 3007 ◽

Cited By ~ 5

Author(s):

Junya Yoshioka ◽

Yu Ohsugi ◽

Toru Yoshitomi ◽

Tomoyuki Yasukawa ◽

Naoki Sasaki ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Gradient Method ◽

Label Free ◽

Rapid Separation ◽

Isolation System ◽

Tissue Samples ◽

Cell Based Therapy

Bone marrow-derived mesenchymal stem cells (BMSCs) are an important cell resource for stem cell-based therapy, which are generally isolated and enriched by the density-gradient method based on cell size and density after collection of tissue samples. Since this method has limitations with regards to purity and repeatability, development of alternative label-free methods for BMSC separation is desired. In the present study, rapid label-free separation and enrichment of BMSCs from a heterogeneous cell mixture with bone marrow-derived promyelocytes was successfully achieved using a dielectrophoresis (DEP) device comprising saw-shaped electrodes. Upon application of an electric field, HL-60 cells as models of promyelocytes aggregated and floated between the saw-shaped electrodes, while UE7T-13 cells as models of BMSCs were effectively captured on the tips of the saw-shaped electrodes. After washing out the HL-60 cells from the device selectively, the purity of the UE7T-13 cells was increased from 33% to 83.5% within 5 min. Although further experiments and optimization are required, these results show the potential of the DEP device as a label-free rapid cell isolation system yielding high purity for rare and precious cells such as BMSCs.

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Stem cell-based therapy for Parkinson’s disease with a focus on human endometrium-derived mesenchymal stem cells

Journal of Cellular Physiology ◽

10.1002/jcp.27182 ◽

2018 ◽

Vol 234 (2) ◽

pp. 1326-1335 ◽

Cited By ~ 12

Author(s):

Saeid Bagheri-Mohammadi ◽

Mohammad Karimian ◽

Behrang Alani ◽

Javad Verdi ◽

Rana Moradian Tehrani ◽

...

Keyword(s):

Parkinson’S Disease ◽

Stem Cells ◽

Parkinson's Disease ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Human Endometrium ◽

Cell Based Therapy

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The concurrent therapeutic potential of adipose-derived mesenchymal stem cells on Gentamycin-induced hepatorenal toxicity in rats

Current Stem Cell Research & Therapy ◽

10.2174/1574888x16666211011124154 ◽

2021 ◽

Vol 16 ◽

Author(s):

Mohamed A Rawash ◽

Ayman Saber Mohamed ◽

Emad M El-Zayat

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Uric Acid ◽

Stem Cell ◽

Kidney Disease ◽

Therapeutic Potential ◽

Daily Injection ◽

Adipose Mesenchymal Stem Cells ◽

Liver And Kidney ◽

Therapy Option

Background: Adipose mesenchymal stem cells (AMSCs) are a type of stem cell employed to repair damaged organs. This study aimed to see how effective AMSCs are at treating gentamycin-induced hepatorenal damage in rats. Methods: 18 male Wister rats were assigned into three groups; control, Gentamycin (GM), and GM+AMSCs. GM induced hepatorenal toxicity through daily injection (100 mg/kg, i.p.) for eight days. On day 9, AMSC (106 cells/ml/rat) was injected intravenously. Results : Creatinine, urea, uric acid, AST, ALP, ALT, TNF-, and MDA levels decreased, whereas IL-10, GSH, and CAT levels increased, indicating the therapeutic potency of intravenous injection AMSCs. Conclusion: The current study demonstrated the simultaneous therapeutic efficacy of adipose mesenchymal stem cells on the liver and kidney in the treatment of Gentamycin-induced hepatotoxicity. These data show that AMSCs could be a feasible therapy option for liver and kidney disease.

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Glutathione–Allylsulfur Conjugates as Mesenchymal Stem Cells Stimulating Agents for Potential Applications in Tissue Repair

International Journal of Molecular Sciences ◽

10.3390/ijms21051638 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1638 ◽

Cited By ~ 1

Author(s):

Emilia Di Giovanni ◽

Silvia Buonvino ◽

Ivano Amelio ◽

Sonia Melino

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Tissue Repair ◽

Dermal Fibroblasts ◽

Water Soluble ◽

Dependent Manner ◽

Tissue Repair And Regeneration ◽

Stem Cell Delivery ◽

Cell Based Therapy

The endogenous gasotransmitter H2S plays an important role in the central nervous, respiratory and cardiovascular systems. Accordingly, slow-releasing H2S donors are powerful tools for basic studies and innovative pharmaco-therapeutic agents for cardiovascular and neurodegenerative diseases. Nonetheless, the effects of H2S-releasing agents on the growth of stem cells have not been fully investigated. H2S preconditioning can enhance mesenchymal stem cell survival after post-ischaemic myocardial implantation; therefore, stem cell therapy combined with H2S may be relevant in cell-based therapy for regenerative medicine. Here, we studied the effects of slow-releasing H2S agents on the cell growth and differentiation of cardiac Lin− Sca1+ human mesenchymal stem cells (cMSC) and on normal human dermal fibroblasts (NHDF). In particular, we investigated the effects of water-soluble GSH–garlic conjugates (GSGa) on cMSC compared to other H2S-releasing agents, such as Na2S and GYY4137. GSGa treatment of cMSC and NHDF increased their cell proliferation and migration in a concentration dependent manner with respect to the control. GSGa treatment promoted an upregulation of the expression of proteins involved in oxidative stress protection, cell–cell adhesion and commitment to differentiation. These results highlight the effects of H2S-natural donors as biochemical factors that promote MSC homing, increasing their safety profile and efficacy after transplantation, and the value of these donors in developing functional 3D-stem cell delivery systems for cardiac muscle tissue repair and regeneration.

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Chronic Toxicity Test in Cynomolgus Monkeys For 98 Days with Repeated Intravenous Infusion of Cynomolgus Umbilical Cord Mesenchymal Stem Cells

Cellular Physiology and Biochemistry ◽

10.1159/000481639 ◽

2017 ◽

Vol 43 (3) ◽

pp. 891-904 ◽

Cited By ~ 2

Author(s):

Jie He ◽

Guang-ping Ruan ◽

Xiang Yao ◽

Ju-fen Liu ◽

Xiang-qing Zhu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Umbilical Cord ◽

Intravenous Infusion ◽

Dose Group ◽

High Dose ◽

Human Umbilical Cord ◽

Cynomolgus Monkeys ◽

Cell Based Therapy

Background/Aims: Stem cell-based therapy is attractive in many clinical studies, but current data on the safety of stem cell applications remains inadequate. This study observed the safety, immunological effect of cynomolgus monkey umbilical cord mesenchymal stem cells (mUC-MSCs) injected into cynomolgus monkeys, in order to evaluate the safety of human umbilical cord mesenchymal stem cells (hUC-MSCs) prepared for human clinical application. Methods: Eighteen cynomolgus monkeys were divided into three groups. Group 1 is control group, Group 2 is low-dose group, Group 3 is high-dose group. After repeated administrations of mUC-MSCs, cynomolgus monkeys were observed for possible toxic reactions. Results: During the experiment, no animal died. There were no toxicological abnormalities in body weight, body temperature, electrocardiogram, coagulation and pathology. In the groups 2 and 3, AST and CK transiently increased, and serum inorganic P slightly decreased. All animals were able to recover at 28 days after the infusion was stopped. In the groups 2 and 3, CD3+ and IL-6 levels significantly increased, and recovery was after 28 days of infusion. There were no obvious pathological changes associated with the infusion of cells in the general and microscopic examinations. Conclusions: The safe dosage of repeated intravenous infusion of mUC-MSCs in cynomolgus monkeys is 1.0 × 107/kg, which is 10 times of that in clinical human use.

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