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

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.

Download Full-text

Mesenchymal Stem Cell Therapy in Stroke: A Systematic Review of Literature in Pre-Clinical and Clinical Research

Cell Transplantation ◽

10.1177/0963689718806846 ◽

2018 ◽

Vol 27 (12) ◽

pp. 1723-1730 ◽

Cited By ~ 19

Author(s):

Haiqing Zheng ◽

Bin Zhang ◽

Pratik Y. Chhatbar ◽

Yi Dong ◽

Ali Alawieh ◽

...

Keyword(s):

Systematic Review ◽

Stem Cells ◽

Stem Cell ◽

Cell Therapy ◽

Stem Cell Therapy ◽

Clinical Studies ◽

Animal Studies ◽

Current Evidence ◽

Human Trials

Exogenous stem cell therapy (SCT) has been recognized recently as a promising neuroregenerative strategy to augment recovery in stroke survivors. Mesenchymal stem cells (MSCs) are the primary source of stem cells used in the majority of both pre-clinical and clinical studies in stroke. In the absence of evidence-based guidelines on the use of SCT in stroke patients, understanding the progress of MSC research across published studies will assist researchers and clinicians in better achieving success in translating research. We conducted a systematic review on published literature using MSCs in both pre-clinical studies and clinical trials between 2008 and 2017 using the public databases PubMed and Ovid Medline, and the clinical trial registry ( www.clinicaltrials.gov ). A total of 78 pre-clinical studies and eight clinical studies were identified. While majority of the pre-clinical and clinical studies demonstrated statistically significant effects, the clinical significance of these findings was still unclear. Effect sizes could not be measured mainly due to reporting issues in pre-clinical studies, thus limiting our ability to compare results across studies quantitatively. The overall quality of both pre-clinical and clinical studies was sub-optimal. By conducting a systematic review of both pre-clinical and clinical studies on MSCs therapy in stroke, we assessed the quality of current evidence and identified several issues and gaps in translating animal studies to human trials. Addressing these issues and incorporating changes into future animal studies and human trials may lead to better success of stem cells-based therapeutics in the near future.

Download Full-text

Efficacy and Safety of Regimens Used for the Treatment of POEMS Syndrome- a Systematic Review

Blood ◽

10.1182/blood-2020-141078 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 7-7

Author(s):

Unaiza Faizan ◽

Muhammad Saad Farooqi ◽

Hassaan Imtiaz ◽

Muhammad Yasir Anwar ◽

Muhammad Khawar Sana ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Clinical Studies ◽

Case Series ◽

Poems Syndrome ◽

Efficacy And Safety ◽

Phase I Clinical Trials ◽

Myeloma Protein ◽

Neurological Response ◽

Grade 3

Introduction: POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy/edema, myeloma protein, skin changes) is a rare disorder associated with plasma cell neoplasia where an overproduction of proinflammatory cytokines such as vascular endothelial growth factor (VEGF) upregulates vasculogenesis and increases vascular permeability resulting in multiple symptoms of the disease e.g. edema and hemangioma. Although the limited-stage disease can be treated with radiotherapy, treatment for the more advanced disease remains unclear. Here we offer a systematic review of the efficacy and safety of treatment regimens used to treat POEMS syndrome in the adult population. Methods: Databases i.e. PubMed, Embase, Web of Science, and clinicaltrials.gov were searched since inception through May 15th, 2020, following the PRISMA guidelines. Out of 421 studies, 8 articles (5 prospective clinical trials, and 3 retrospective studies) were included. Phase I clinical trials, abstracts, case reports, case series, and review articles were excluded. Results: A total of 171 patients (21-79 years of age) were evaluated in 8 clinical studies. Immunomodulator Based Regimens: In the 5 clinical studies (N=96) where lenalidomide (Len) plus dexamethasone (Dex) were used, the hematological (heme) complete response (CR) ranged from 20% to 46%. Heme CR was defined as the absence of monoclonal immunoglobulins in serum or urine. VEGF CR defined as normalization of serum VEGF levels ranged from 35% to 80%. Neurological response defined as the improvement in the overall neuropathy limitations scale (ONLS) by at least one score ranged from 0% to 95%. These studies reported 2-3 year progression-free survival (PFS) and overall survival (OS) of 59% to 92% and 90% to 100%, respectively. In the study by Suichi et al. (N=5), VEGF CR was reported to be 80%. However, no neurological improvement was seen in these patients. Proteasome Inhibitor Based Regimens: In the study by He et al. (N=20) bortezomib in combination with cyclophosphamide and Dex yielded heme, VEGF, and neurological responses in 76%, 88%, and 95% of the patients, respectively. No grade ≥3 treatment-related adverse effects (TRAE) were seen. Conventional Chemotherapy Based Regimens: In the phase II trial conducted by Misawa et al. (N=25) the reduction in serum VEGF levels, as well as clinical response as measured by improvement in muscle strength, was higher in the thalidomide arm as compared to the placebo arm. Grade ≥3 TRAE reported in the treatment arm were cardiac arrest, heart failure, and dehydration in 1 (8%) patient each. In the study by Li et al. (N=31) melphalan (Mel) in combination with Dex achieved heme, VEGF, and neurological response rates of 81%, 100%, and 100%, respectively. Twenty percent of the patients experienced grade ≥3 TRAE. Conclusion: Immunomodulator and chemotherapy based regimens appear to have a reasonable safety and efficacy profile. Lenalidomide and melphalan based therapies were most effective. Proteasome inhibitors based regimens yielded efficacious results without significant toxicity. More studies with existing and newer combinations with autologous stem cell transplantation are warranted. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Download Full-text

Stem Cells as a Model of Study of SARS-CoV-2 and COVID-19: A Systematic Review of the Literature

BioMed Research International ◽

10.1155/2021/9915927 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

María Verónica Cuevas-Gonzalez ◽

Álvaro Garcia-Perez ◽

Álvaro Edgar Gonzalez-Aragon Pineda ◽

León Francisco Espinosa-Cristobal ◽

Alejandro Donohue-Cornejo ◽

...

Keyword(s):

Stem Cells ◽

Clinical Trials ◽

Stem Cell ◽

Clinical Studies ◽

Case Series ◽

In Vitro Studies ◽

In Vivo Studies

Background. The SARS-CoV-2 virus is the cause of the latest pandemic of the 21st century; it is responsible for the development of COVID-19. Within the multiple study models for both the biology and the treatment of SARS-CoV-2, the use of stem cells has been proposed because of their ability to increase the immune response and to repair tissue. Therefore, the objective of this review is to evaluate the role of stem cells against SARS-CoV-2 and COVID-19 in order to identify their potential as a study model and as a possible therapeutic source against tissue damage caused by this virus. Therefore, the following research question was established: What is the role of stem cells in the study of SARS-CoV-2 and the treatment of COVID-19? Materials and Methods. A search was carried out in the electronic databases of PUBMED, Scopus, and ScienceDirect. The following keywords were used: “SARS-CoV-2,” “COVID-19,” and “STEM CELL,” plus independent search strategies with the Boolean operators “OR” and “AND.” The identified reports were those whose main objective was the study of stem cells in relation to SARS-CoV-2 or COVID-19. For the development of this study, the following inclusion criteria were taken into account: studies whose main objective was the study of stem cells in relation to SARS-CoV-2 or COVID-19 and clinical case studies, case reports, clinical trials, pilot studies, in vitro, or in vivo studies. For assessment of the risk of bias for in vitro studies, the SciRAP tool was used. The data collected for each type of study, clinical or in vitro, were analyzed with descriptive statistics using the SPSS V.22 program. Results. Of the total of studies included ( n = 39 ), 22 corresponded to in vitro investigations and 17 to human studies (clinical cases ( n = 9 ), case series ( n = 2 ), pilot clinical trials ( n = 5 ), clinical trials ( n = 1 )). In vitro studies that induced pluripotent stem cells were the most used ( n = 12 ), and in clinical studies, the umbilical stem cells derived were the most reported ( n = 11 ). The mean age of the study subjects was 58.3 years. After the application of stem cell therapy, the follow-up period was 8 days minimum and 90 days maximum. Discussion. The mechanism by which the virus enters the cell is through protein “S,” located on the surface of the membrane, by recognizing the ACE2 receptor located on the target cell. The evidence that the expression of ACE2 and TMPRSS2 in stem cells indicates that stem cells from bone marrow and amniotic fluid have very little expression. This shows that stem cell has a low risk of infection with SARS-CoV-2. Conclusion. The use of stem cells is a highly relevant therapeutic option. It has been shown in both in vitro studies and clinical trials that it counteracts the excessive secretion of cytokines. There are even more studies that focus on long-term follow-up; thus, the potential for major side effects can be analyzed more clearly. Finally, the ethical use of stem cells from fetal or infant origin needs to be regulated. The study was registered in PROSPERO (no. CRD42021229038). The limitations of the study were because of the methodology employed, the sample was not very large, and the follow-up period of the clinical studies was relatively short.

Download Full-text

Stem Cell Therapy for Chronic Pain Management: Review of Uses, Advances, and Adverse Effects

January 2018 - Pain Physician ◽

10.36076/ppj.2017.305 ◽

2017 ◽

Vol 4 (20;4) ◽

pp. 293-305 ◽

Cited By ~ 12

Author(s):

Krishnan Chakravarthy

Keyword(s):

Stem Cells ◽

Chronic Pain ◽

Clinical Trials ◽

Neuropathic Pain ◽

Stem Cell ◽

Pain Management ◽

Cell Therapy ◽

Treatment Modalities ◽

Chronic Pain Management ◽

Cell Based Therapy

Background: This review article outlines the recent advances, uses, and adverse effects of cell-based therapy for chronic pain management. Cell based therapies are gaining increasing ground as novel treatment modalities for a variety of pain pathologies that include, but are not limited to, neuropathic pain and degenerative disc disease. As these treatment modalities become more common practice, we have focused our review to provide pain practitioners and other practicing physicians an understanding of the technology and to summarize key clinical data and existing clinical trials that are being pursued by clinical investigators worldwide. Objective: Review of stem cell technology and applications in pain management. Study Design: Narrative review. Methods: The Pubmed NCBI and EMBASE databases was utilized to review published reports of clinical studies reported from 2000 to 2015, and ClinicalTrials.gov (www. clinicaltrials.gov/ct2/search) search function was used to document ongoing clinical trials [keywords: “chronic pain,” “disc pain,” “cell therapy,” “osteoarthritis,” “neuropathic,” “stem cell”] currently active and recruiting patients. Results: Articles were screened by title, abstract, and full article review. They were then analyzed by specific clinical indications and appropriate data were presented based on critical analysis of those articles. Limitations: More studies looking at the systematic use of stem cells in pain management will be required to draw conclusions about the benefits of the technology. Conclusion: Though the data from existing studies look promising for the use of stem cells as a novel therapeutic strategy for discogenic pain, neuropathic pain, and osteoarthritis, additional clinical studies will be needed to validate the benefit of the technology for clinical use. However, we hope that this narrative review will help guide pain physicians in making informed decisions for their patients about the potential of cell-based therapy for treating chronic pain conditions. Key words: Stem cell therapy, chronic pain, clinical trials, disc pain, neuropathic pain, mesenchymal stem cells, osteoarthritis, pain management

Download Full-text

Preclinical efficacy of stem cell therapy for skin flap: a systematic review and meta-analysis

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02103-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yuan Li ◽

Qi-lin Jiang ◽

Leanne Van der Merwe ◽

Dong-hao Lou ◽

Cai Lin

Keyword(s):

Systematic Review ◽

Stem Cells ◽

Stem Cell ◽

Survival Rate ◽

Meta Analysis ◽

Skin Flap ◽

Cochrane Library ◽

Skin Flaps ◽

Cell Based Therapy ◽

Stem Cell Treatment

Abstract Background A skin flap is one of the most critical surgical techniques for the restoration of cutaneous defects. However, the distal necrosis of the skin flap severely restricts the clinical application of flap surgery. As there is no consensus on the treatment methods to prevent distal necrosis of skin flaps, more effective and feasible interventions to prevent skin flaps from necrosis are urgently needed. Stem therapy as a potential method to improve the survival rate of skin flaps is receiving increasing attention. Methods This review followed the recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statements. Twenty studies with 500 animals were included by searching Web of Science, EMBASE, PubMed, and Cochrane Library databases, up until October 8, 2020. Moreover, the references of the included articles were searched manually to obtain other studies. All analyses were conducted using Review Manager V.5.3 software. Results Meta-analysis of all 20 studies demonstrated stem cell treatment has significant effects on reducing necrosis of skin flap compared with the control group (SMD: 3.20, 95% CI 2.47 to 3.93). Besides, subgroup analysis showed differences in the efficacy of stem cells in improving the survival rate of skin flaps in areas of skin flap, cell type, transplant types, and method of administration of stem cells. The meta-analysis also showed that stem cell treatment had a significant effect on increasing blood vessel density (SMD: 2.96, 95% CI 2.21 to 3.72) and increasing the expression of vascular endothelial growth factor (VEGF, SMD: 4.34, 95% CI 2.48 to 6.1). Conclusions The preclinical evidence of our systematic review indicate that stem cell-based therapy is effective for promoting early angiogenesis by up regulating VEGF and ultimately improving the survival rate of skin flap. In summary, small area skin flap, the administration method of intra-arterial injection, ASCs and MSCs, and xenogenic stem cells from humans showed more effective for the survival of animal skin flaps. In general, stem cell-based therapy may be a promising method to prevent skin flap necrosis.

Download Full-text

Optimizing Stem Cell Therapy after Ischemic Brain Injury

Journal of Stroke ◽

10.5853/jos.2019.03048 ◽

2020 ◽

Vol 22 (3) ◽

pp. 286-305 ◽

Cited By ~ 1

Author(s):

Shuai Zhang ◽

Brittany Bolduc Lachance ◽

Bilal Moiz ◽

Xiaofeng Jia

Keyword(s):

Stem Cells ◽

Clinical Trials ◽

Cardiac Arrest ◽

Stem Cell ◽

Brain Injury ◽

Cell Therapy ◽

Stem Cell Therapy ◽

Ischemic Brain Injury ◽

Ischemic Brain ◽

Injury Treatment

Stem cells have been used for regenerative and therapeutic purposes in a variety of diseases. In ischemic brain injury, preclinical studies have been promising, but have failed to translate results to clinical trials. We aimed to explore the application of stem cells after ischemic brain injury by focusing on topics such as delivery routes, regeneration efficacy, adverse effects, and in vivo potential optimization. PUBMED and Web of Science were searched for the latest studies examining stem cell therapy applications in ischemic brain injury, particularly after stroke or cardiac arrest, with a focus on studies addressing delivery optimization, stem cell type comparison, or translational aspects. Other studies providing further understanding or potential contributions to ischemic brain injury treatment were also included. Multiple stem cell types have been investigated in ischemic brain injury treatment, with a strong literature base in the treatment of stroke. Studies have suggested that stem cell administration after ischemic brain injury exerts paracrine effects via growth factor release, blood-brain barrier integrity protection, and allows for exosome release for ischemic injury mitigation. To date, limited studies have investigated these therapeutic mechanisms in the setting of cardiac arrest or therapeutic hypothermia. Several delivery modalities are available, each with limitations regarding invasiveness and safety outcomes. Intranasal delivery presents a potentially improved mechanism, and hypoxic conditioning offers a potential stem cell therapy optimization strategy for ischemic brain injury. The use of stem cells to treat ischemic brain injury in clinical trials is in its early phase; however, increasing preclinical evidence suggests that stem cells can contribute to the down-regulation of inflammatory phenotypes and regeneration following injury. The safety and the tolerability profile of stem cells have been confirmed, and their potent therapeutic effects make them powerful therapeutic agents for ischemic brain injury patients.

Download Full-text

Regenerative Cardiovascular Therapies: Stem Cells and Beyond

International Journal of Molecular Sciences ◽

10.3390/ijms20061420 ◽

2019 ◽

Vol 20 (6) ◽

pp. 1420 ◽

Cited By ~ 17

Author(s):

Bernhard Wernly ◽

Moritz Mirna ◽

Richard Rezar ◽

Christine Prodinger ◽

Christian Jung ◽

...

Keyword(s):

Stem Cells ◽

Clinical Trials ◽

Stem Cell ◽

Cell Therapy ◽

Stem Cell Therapy ◽

Basic Science ◽

Left Ventricular ◽

Specific Cell ◽

Therapeutic Effects ◽

Cell Processing

Although reperfusion therapy has improved outcomes, acute myocardial infarction (AMI) is still associated with both significant mortality and morbidity. Once irreversible myocardial cell death due to ischemia and reperfusion sets in, scarring leads to reduction in left ventricular function and subsequent heart failure. Regenerative cardiovascular medicine experienced a boost in the early 2000s when regenerative effects of bone marrow stem cells in a murine model of AMI were described. Translation from an animal model to stem cell application in a clinical setting was rapid and the first large trials in humans suffering from AMI were conducted. However, high initial hopes were early shattered by inconsistent results of randomized clinical trials in patients suffering from AMI treated with stem cells. Hence, we provide an overview of both basic science and clinical trials carried out in regenerative cardiovascular therapies. Possible pitfalls in specific cell processing techniques and trial design are discussed as these factors influence both basic science and clinical outcomes. We address possible solutions. Alternative mechanisms and explanations for effects seen in both basic science and some clinical trials are discussed here, with special emphasis on paracrine mechanisms via growth factors, exosomes, and microRNAs. Based on these findings, we propose an outlook in which stem cell therapy, or therapeutic effects associated with stem cell therapy, such as paracrine mechanisms, might play an important role in the future. Optimizing stem cell processing and a better understanding of paracrine signaling as well as its effect on cardioprotection and remodeling after AMI might improve not only AMI research, but also our patients’ outcomes.

Download Full-text

Exploring the Most Promising Stem Cell Therapy in Liver Failure: A Systematic Review

Stem Cells International ◽

10.1155/2019/2782548 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 4

Author(s):

Jeanne AdiwinataPawitan

Keyword(s):

Systematic Review ◽

Stem Cells ◽

Stem Cell ◽

Cell Therapy ◽

Liver Failure ◽

Stem Cell Therapy ◽

Adult Stem Cells ◽

Cochrane Library ◽

Safety And Efficacy ◽

Alternative Approaches

Background. Alternative approaches to transplantation for liver failure are needed. One of the alternative approaches is stem cell therapy. However, stem cell therapy in liver failure is not standardized yet, as every centre have their own methods. This systematic review is aimed at compiling and analyzing the various studies that use stem cells to treat liver failure, to get an insight into potential protocols in terms of safety and efficacy by comparing them to controls. Methods. This systematic review was done according to PRISMA guidelines and submitted for registration in PROSPERO (registration number CRD42018106119). All published studies in PubMed/MEDLINE and Cochrane Library, using key words: “human” and “stem cell” AND “liver failure” on 16th June 2018, without time restriction. In addition, relevant articles that are found during full-text search were added. Inclusion criteria included all original articles on stem cell use in humans with liver failure. Data collected included study type, treatment and control number, severity of disease, concomitant therapy, type and source of cells, passage of cells, dose, administration route, repeats, and interval between repeats, outcomes, and adverse events compared to controls. Data were analyzed descriptively to determine the possible causes of adverse reactions, and which protocols gave a satisfactory outcome, in terms of safety and efficacy. Results. There were 25 original articles, i.e., eight case studies and 17 studies with controls. Conclusion. Among the various adult stem cells that were used in human studies, MSCs from the bone marrow or umbilical cord performed better compared to other types of adult stem cells, though no study showed a complete and sustainable performance in the outcome measures. Intravenous (IV) route was equal to invasive route. Fresh or cryopreserved, and autologous or allogeneic MSCs were equally beneficial; and giving too many cells via intraportal or the hepatic artery might be counterproductive.

Download Full-text

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

International Journal of Molecular Sciences ◽

10.3390/ijms21155467 ◽

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.

Download Full-text

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.

Download Full-text