scholarly journals Perspective on Stem Cell Therapy in Organ Fibrosis: Animal Models and Human Studies

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1068
Author(s):  
Joanna Wiśniewska ◽  
Agnieszka Sadowska ◽  
Anna Wójtowicz ◽  
Magda Słyszewska ◽  
Anna Szóstek-Mioduchowska
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Animal Models ◽  
The Body ◽  
Preclinical Studies ◽  
Cell Based Therapy ◽  
Fibrotic Diseases ◽  
Fibrotic Disorders ◽  
Organ Fibrosis

Tissue fibrosis is characterized by excessive deposition of extracellular matrix (ECM) components that result from the disruption of regulatory processes responsible for ECM synthesis, deposition, and remodeling. Fibrosis develops in response to a trigger or injury and can occur in nearly all organs of the body. Thus, fibrosis leads to severe pathological conditions that disrupt organ architecture and cause loss of function. It has been estimated that severe fibrotic disorders are responsible for up to one-third of deaths worldwide. Although intensive research on the development of new strategies for fibrosis treatment has been carried out, therapeutic approaches remain limited. Since stem cells, especially mesenchymal stem cells (MSCs), show remarkable self-renewal, differentiation, and immunomodulatory capacity, they have been intensively tested in preclinical studies and clinical trials as a potential tool to slow down the progression of fibrosis and improve the quality of life of patients with fibrotic disorders. In this review, we summarize in vitro studies, preclinical studies performed on animal models of human fibrotic diseases, and recent clinical trials on the efficacy of allogeneic and autologous stem cell applications in severe types of fibrosis that develop in lungs, liver, heart, kidney, uterus, and skin. Although the results of the studies seem to be encouraging, there are many aspects of cell-based therapy, including the cell source, dose, administration route and frequency, timing of delivery, and long-term safety, that remain open areas for future investigation. We also discuss the contemporary status, challenges, and future perspectives of stem cell transplantation for therapeutic options in fibrotic diseases as well as we present recent patents for stem cell-based therapies in organ fibrosis.

scholarly journals Mesenchymal stem cell-derived extracellular vesicles in therapy against fibrotic diseases

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuling Huang ◽  
Lina Yang
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Preclinical Studies ◽  
Preclinical Research ◽  
Existing Problems ◽  
Fibrotic Diseases

AbstractFibrosis is likely to occur in many tissues and organs to induce cicatrisation and dysfunction. The therapeutic regimens for delaying and even reversing fibrosis are quite limited at present. In nearly a decade, mesenchymal stem cells (MSCs) have been widely acknowledged as useful in treating fibrotic diseases in preclinical and clinical trials. Further preclinical studies indicated that the effects of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are probably superior to that of MSCs. At present, MSC-EVs have attracted much attention in treating fibrosis of lung, liver, kidney, skin, and heart. By contrast, a significant knowledge-gap remains in treating fibrosis of other tissues and organs (including uterus, gastrointestinal tract, and peritoneum) with the aid of MSC-EVs. This review summarises the preclinical research status of MSC-EVs in treating fibrotic diseases and proposes solutions to existing problems, which contribute to further clinical research on the treatment of fibrotic diseases with MSC-EVs in the future.

scholarly journals Regenerative potential of secretome from dental stem cells: a systematic review of preclinical studies

2018 ◽  
Vol 29 (3) ◽  
pp. 321-332 ◽  
Author(s):  
Suleiman Alhaji Muhammad ◽  
Norshariza Nordin ◽  
Sharida Fakurazi
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Stem Cell ◽  
Animal Models ◽  
Conditioned Medium ◽  
Tissue Regeneration ◽  
Therapeutic Benefit ◽  
Risk Of Bias ◽  
Preclinical Studies

AbstractInjury to tissues is a major clinical challenge due to the limited regenerative capacity of endogenous cells. Stem cell therapy is evolving rapidly as an alternative for tissue regeneration. However, increasing evidence suggests that the regenerative ability of stem cells is mainly mediated by paracrine actions of secretome that are generally secreted by the cells. We aimed to systematically evaluate the efficacy of dental stem cell (DSC)-conditioned medium inin vivoanimal models of various tissue defects. A total of 15 eligible studies was included by searching Pubmed, Scopus and Medline databases up to August 2017. The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation risk of bias tool. Of 15 studies, seven reported the therapeutic benefit of the conditioned medium on neurological diseases and three reported on joint/bone-related defects. Two interventions were on liver diseases, whereas the remaining three addressed myocardial infarction and reperfusion, lung injury and diabetes. Nine studies were performed using mouse models and the remaining six studies used rat models. The methodological quality of the studies was low, as most of the key elements required in reports of preclinical studies were not reported. The findings of this review suggested that conditioned medium from DSCs improved tissue regeneration and functional recovery. This current review strengthens the therapeutic benefit of cell-free product for tissue repair in animal models. A well-planned study utilizing validated outcome measures and long-term safety studies are required for possible translation to clinical trials.

Stem Cells and Tissue Engineering Techniques

2013 ◽  
Vol 80 (1) ◽  
pp. 11-19
Author(s):  
Gigliola Sica
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Urinary Tract ◽  
Animal Models ◽  
Embryonic Stem ◽  
Cell Types ◽  
Ethical Concerns ◽  
Neoplastic Lesions

The therapeutic use of stem cells and tissue engineering techniques are emerging in urology. Here, stem cell types, their differentiating potential and fundamental characteristics are illustrated. The cancer stem cell hypothesis is reported with reference to the role played by stem cells in the origin, development and progression of neoplastic lesions. In addition, recent reports of results obtained with stem cells alone or seeded in scaffolds to overcome problems of damaged urinary tract tissue are summarized. Among others, the application of these biotechnologies in urinary bladder, and urethra are delineated. Nevertheless, apart from the ethical concerns raised from the use of embryonic stem cells, a lot of questions need to be solved concerning the biology of stem cells before their widespread use in clinical trials. Further investigation is also required in tissue engineering utilizing animal models.

scholarly journals Induced Pluripotent Stem Cells: Hope in the Treatment of Diseases, including Muscular Dystrophies

2020 ◽  
Vol 21 (15) ◽  
pp. 5467
Author(s):  
Daniela Gois Beghini ◽  
Samuel Iwao Horita ◽  
Cynthia Machado Cascabulho ◽  
Luiz Anastácio Alves ◽  
Andrea Henriques-Pons
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Ips Cells ◽  
High Plasticity ◽  
Cell Based Therapy ◽  
Induced Pluripotent

Induced pluripotent stem (iPS) cells are laboratory-produced cells that combine the biological advantages of somatic adult and stem cells for cell-based therapy. The reprogramming of cells, such as fibroblasts, to an embryonic stem cell-like state is done by the ectopic expression of transcription factors responsible for generating embryonic stem cell properties. These primary factors are octamer-binding transcription factor 4 (Oct3/4), sex-determining region Y-box 2 (Sox2), Krüppel-like factor 4 (Klf4), and the proto-oncogene protein homolog of avian myelocytomatosis (c-Myc). The somatic cells can be easily obtained from the patient who will be subjected to cellular therapy and be reprogrammed to acquire the necessary high plasticity of embryonic stem cells. These cells have no ethical limitations involved, as in the case of embryonic stem cells, and display minimal immunological rejection risks after transplant. Currently, several clinical trials are in progress, most of them in phase I or II. Still, some inherent risks, such as chromosomal instability, insertional tumors, and teratoma formation, must be overcome to reach full clinical translation. However, with the clinical trials and extensive basic research studying the biology of these cells, a promising future for human cell-based therapies using iPS cells seems to be increasingly clear and close.

scholarly journals Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures

2018 ◽  
Vol 2018 ◽  
pp. 1-22 ◽  
Author(s):  
Melissa Lo Monaco ◽  
Greet Merckx ◽  
Jessica Ratajczak ◽  
Pascal Gervois ◽  
Petra Hilkens ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Animal Models ◽  
Outcome Measures ◽  
Cartilage Repair ◽  
Cartilage Tissue ◽  
Preclinical Studies ◽  
Paracrine Factors ◽  
Advantages And Disadvantages

Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recentin vitrodata and fromin vivopreclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.

scholarly journals Stem cell sources and therapeutic approaches for central nervous system and neural retinal disorders

2008 ◽  
Vol 24 (3-4) ◽  
pp. E11 ◽  
Author(s):  
Diana Yu ◽  
Gabriel A. Silva
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Stem Cell ◽  
Neurodegenerative Diseases ◽  
The Body ◽  
Cns Disorders ◽  
Cell Based Therapy ◽  
Therapeutic Benefits ◽  
Made In

✓ In the past decades, stem cell biology has made a profound impact on our views of mammalian development as well as opened new avenues in regenerative medicine. The potential of stem cells to differentiate into various cell types of the body is the principal reason they are being explored in treatments for diseases in which there may be dysfunctional cells and/or loss of healthy cells due to disease. In addition, other properties are unique to stem cells; their endogenous trophic support, ability to home to sites of pathological entities, and stability in culture, which allows genetic manipulation, are also being utilized to formulate stem cell–based therapy for central nervous system (CNS) disorders. In this review, the authors will review key characteristics of embryonic and somatic (adult) stem cells, consider therapeutic strategies employed in stem cell therapy, and discuss the recent advances made in stem cell–based therapy for a number of progressive neurodegenerative diseases in the CNS as well as neuronal degeneration secondary to other abnormalities and injuries. Although a great deal of progress has been made in our knowledge of stem cells and their utility in treating CNS disorders, much still needs to be elucidated regarding the biology of the stem cells and the pathogenesis of targeted CNS diseases to maximize therapeutic benefits. Nonetheless, stem cells present tremendous promise in the treatment of a variety of neurodegenerative diseases.

scholarly journals Therapeutic Potential of Human Stem Cell Implantation in Alzheimer’s Disease

2021 ◽  
Vol 22 (18) ◽  
pp. 10151
Author(s):  
Hau Jun Chan ◽  
Yanshree ◽  
Jaydeep Roy ◽  
George Lim Tipoe ◽  
Man-Lung Fung ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Therapeutic Potential ◽  
Morris Water Maze Test ◽  
Preclinical Studies

Alzheimer’s disease (AD) is a progressive debilitating neurodegenerative disease and the most common form of dementia in the older population. At present, there is no definitive effective treatment for AD. Therefore, researchers are now looking at stem cell therapy as a possible treatment for AD, but whether stem cells are safe and effective in humans is still not clear. In this narrative review, we discuss both preclinical studies and clinical trials on the therapeutic potential of human stem cells in AD. Preclinical studies have successfully differentiated stem cells into neurons in vitro, indicating the potential viability of stem cell therapy in neurodegenerative diseases. Preclinical studies have also shown that stem cell therapy is safe and effective in improving cognitive performance in animal models, as demonstrated in the Morris water maze test and novel object recognition test. Although few clinical trials have been completed and many trials are still in phase I and II, the initial results confirm the outcomes of the preclinical studies. However, limitations like rejection, tumorigenicity, and ethical issues are still barriers to the advancement of stem cell therapy. In conclusion, the use of stem cells in the treatment of AD shows promise in terms of effectiveness and safety.

Moral obligations in conducting stem cell-based therapy trials for autism spectrum disorder

2021 ◽  
pp. medethics-2020-107106
Author(s):  
Nicole Shu Ling Yeo-Teh ◽  
Bor Luen Tang
Keyword(s):  
Autism Spectrum Disorder ◽  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Therapeutic Benefit ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Moral Obligations ◽  
Direct To Consumer ◽  
Cell Based Therapy

Unregulated patient treatments and approved clinical trials have been conducted with haematopoietic stem cells and mesenchymal stem cells for children with autism spectrum disorder (ASD). While the former direct-to-consumer practice is usually considered rogue and should be legally constrained, regulated clinical trials could also be ethically questionable. Here, we outline principal objections against these trials as they are currently conducted. Notably, these often lack a clear rationale for how transplanted cells may confer a therapeutic benefit in ASD, and thus, have ill-defined therapeutic outcomes. We posit that ambiguous and unsubstantiated descriptions of outcome from such clinical trials may nonetheless appeal to the lay public as being based on authentic scientific findings. These may further fuel caregivers of patients with ASD to pursue unregulated direct-to-consumer treatments, thus exposing them to unnecessary risks. There is, therefore, a moral obligation on the part of those regulating and conducting clinical trials of stem cell-based therapeutic for ASD minors to incorporate clear therapeutic targets, scientific rigour and reporting accuracy in their work. Any further stem cell-based trials for ASD unsupported by significant preclinical advances and particularly sound scientific hypothesis and aims would be ethically indefensible.

scholarly journals Dental Tissue-Derived Human Mesenchymal Stem Cells and Their Potential in Therapeutic Application

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Lu Gan ◽  
Ying Liu ◽  
Dixin Cui ◽  
Yue Pan ◽  
Liwei Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Preclinical Studies ◽  
Dental Tissue ◽  
Differentiation Potential ◽  
Dental Tissues ◽  
Lineage Differentiation ◽  
Cell Based Therapy

Human mesenchymal stem cells (hMSCs) are multipotent cells, which exhibit plastic adherence, express specific cell surface marker spectrum, and have multi-lineage differentiation potential. These cells can be obtained from multiple tissues. Dental tissue-derived hMSCs (dental MSCs) possess the ability to give rise to mesodermal lineage (osteocytes, adipocytes, and chondrocytes), ectodermal lineage (neurocytes), and endodermal lineages (hepatocytes). Dental MSCs were first isolated from dental pulp of the extracted third molar and till now they have been purified from various dental tissues, including pulp tissue of permanent teeth and exfoliated deciduous teeth, apical papilla, periodontal ligament, gingiva, dental follicle, tooth germ, and alveolar bone. Dental MSCs are not only easily accessible but are also expandable in vitro with relative genomic stability for a long period of time. Moreover, dental MSCs have exhibited immunomodulatory properties by secreting cytokines. Easy accessibility, multi-lineage differentiation potential, and immunomodulatory effects make dental MSCs distinct from the other hMSCs and an effective tool in stem cell-based therapy. Several preclinical studies and clinical trials have been performed using dental MSCs in the treatment of multiple ailments, ranging from dental diseases to nondental diseases. The present review has summarized dental MSC sources, multi-lineage differentiation capacities, immunomodulatory features, its potential in the treatment of diseases, and its application in both preclinical studies and clinical trials. The regenerative therapeutic strategies in dental medicine have also been discussed.

scholarly journals Stem cell-based therapy for COVID-19 and ARDS: a systematic review

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Gabriele Zanirati ◽  
Laura Provenzi ◽  
Lucas Lobraico Libermann ◽  
Sabrina Comin Bizotto ◽  
Isadora Machado Ghilardi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Cell Therapy ◽  
Clinical Studies ◽  
Case Series ◽  
Potential Candidate ◽  
Phase I Clinical Trials ◽  
Cell Based Therapy

AbstractDespite global efforts to establish effective interventions for coronavirus disease 2019 (COVID-19) and its major complications, such as acute respiratory distress syndrome (ARDS), the treatment remains mainly supportive. Hence, identifying an effective and safe therapy for severe COVID-19 is critical for saving lives. A significant number of cell-based therapies have been through clinical investigation. In this study, we performed a systematic review of clinical studies investigating different types of stem cells as treatments for COVID-19 and ARDS to evaluate the safety and potential efficacy of cell therapy. The literature search was performed using PubMed, Embase, and Scopus. Among the 29 studies, there were eight case reports, five Phase I clinical trials, four pilot studies, two Phase II clinical trials, one cohort, and one case series. Among the clinical studies, 21 studies used cell therapy to treat COVID-19, while eight studies investigated cell therapy as a treatment for ARDS. Most of these (75%) used mesenchymal stem cells (MSCs) to treat COVID-19 and ARDS. Findings from the analyzed articles indicate a positive impact of stem cell therapy on crucial immunological and inflammatory processes that lead to lung injury in COVID-19 and ARDS patients. Additionally, among the studies, there were no reported deaths causally linked to cell therapy. In addition to standard care treatments concerning COVID-19 management, there has been supportive evidence towards adjuvant therapies to reduce mortality rates and improve recovery of care treatment. Therefore, MSCs treatment could be considered a potential candidate for adjuvant therapy in moderate-to-severe COVID-19 cases and compassionate use.

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