Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: An updated systematic review and meta-analysis

Thompson, Mindi N.; Mei, Shirley H. J.; Wolfe, Dianna; Champagne, Josée; Fergusson, Dean; Stewart, Duncan J.; Sullivan, Katrina; Doxtator, Emily; Lalu, Manoj M.; English, Shane; Granton, John; Hutton, Brian; Marshall, John C.; Maybee, Alies; Walley, Keith R.; Santos, Claudia C. dos; Winston, Brent W.; McIntyre, Lauralyn

doi:10.1016/j.eclinm.2019.100249

Cited by 164 publications

(148 citation statements)

References 64 publications

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“…Indeed, their action is displayed not only in all immune cells, but also in cell populations, such as epithelial cells, endothelial cells, fibroblasts, which take part in inflammatory cascades and are not targeted by other therapies. Moreover, MSCs are an attractive therapeutic option because they elicit no (or a weak) allogeneic immune responses when delivered to a non-identical, non-matched recipient and because they can easily be extracted from a variety of tissues including bone marrow, adipose and placental tissues including umbilical cord blood, and expanded in vitro as well as due to their high safety profile independent to the tissue source and clinical setting [31]. Although they show great promise in the treatment of many immune and inflammatory disorders, the large variability in manufactured cell products, donor cell quality, dosages, formulation as fresh or cryopreserved and differing administration routes have obscured their potential therapeutic benefit.…”

Section: Mscsmentioning

confidence: 99%

Emerging trends in COVID-19 treatment: learning from inflammatory conditions associated with cellular therapies

et al. 2020

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Coronavirus disease 2019 (SARS-CoV2) is an active global health threat for which treatments are desperately being sought. Even though most people infected experience mild to moderate respiratory symptoms and recover with supportive care, certain vulnerable hosts develop severe clinical deterioration. While several drugs are currently being investigated in clinical trials, there are currently no approved treatments or vaccines for COVID-19 and hence there is an unmet need to explore additional therapeutic options. At least three inflammatory disorders or syndromes associated with immune dysfunction have been described in the context of cellular therapy. Specifically, Cytokine Release Syndrome (CRS), Immune Reconstitution Inflammatory Syndrome (IRIS), and Secondary Hemophagocytic Lymphohistiocytosis (sHLH) all have clinical and laboratory characteristics in common with COVID19 and associated therapies that could be worth testing in the context of clinical trials. Here we discuss these diseases, their management, and potential applications of these treatment in the context of COVID-19. We also discuss current cellular therapies that are being evaluated for the treatment of COVID-19 and/or its associated symptoms.

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Section: Mscsmentioning

confidence: 99%

Emerging trends in COVID-19 treatment: learning from inflammatory conditions associated with cellular therapies

et al. 2020

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“…Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in humans has led to an ongoing pandemic of coronavirus disease 2019 (COVID- 19) worldwide. COVID-19 causes a spectrum of clinical illness from mild, moderate, to severe or critical disease.…”

Section: Introductionmentioning

confidence: 99%

Human umbilical cord-derived mesenchymal stem cell therapy in patients with COVID-19: a phase 1 clinical trial

Meng

Wang

et al. 2020

Sig Transduct Target Ther

253

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No effective drug treatments are available for coronavirus disease 2019 (COVID-19). Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage, death, or long-term functional disability in survivors require clinical evaluation. We performed a parallel assigned controlled, non-randomized, phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) infusions in the treatment of patients with moderate and severe COVID-19 pulmonary disease. The study enrolled 18 hospitalized patients with COVID-19 (n = 9 for each group). The treatment group received three cycles of intravenous infusion of UC-MSCs (3 × 10 7 cells per infusion) on days 0, 3, and 6. Both groups received standard COVID-treatment regimens. Adverse events, duration of clinical symptoms, laboratory parameters, length of hospitalization, serial chest computed tomography (CT) images, the PaO 2 /FiO 2 ratio, dynamics of cytokines, and IgG and IgM anti-SARS-CoV-2 antibodies were analyzed. No serious UC-MSCs infusion-associated adverse events were observed. Two patients receiving UC-MSCs developed transient facial flushing and fever, and one patient developed transient hypoxia at 12 h post UC-MSCs transfusion. Mechanical ventilation was required in one patient in the treatment group compared with four in the control group. All patients recovered and were discharged. Our data show that intravenous UC-MSCs infusion in patients with moderate and severe COVID-19 is safe and well tolerated. Phase 2/3 randomized, controlled, double-blinded trials with long-term follow-up are needed to evaluate the therapeutic use of UC-MSCs to reduce deaths and improve long-term treatment outcomes in patients with serious COVID-19.

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“…An advantage of using MSCs as opposed to other drugs to treat acute GVHD is safety, with few, if any side-effects (107,108). There were no side-effects caused by the stromal cells in any of the six children treated with DSCs.…”

Section: Discussionmentioning

confidence: 93%

Mesenchymal Stromal Cells in Pediatric Hematopoietic Cell Transplantation a Review and a Pilot Study in Children Treated With Decidua Stromal Cells for Acute Graft-versus-Host Disease

2020

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Mesenchymal stromal cells (MSCs) are rare precursors in all organs of the body. MSCs have profound anti-inflammatory effects and reduce alloreactivity in vitro and in vivo. In pediatric allogeneic hematopoietic cell transplantation (HCT), MSCs have mainly been used to treat acute graft-versus-host disease (GVHD). MSCs are commercially available for this indication in Canada, Japan, and New Zeeland. More rare indications for MSCs in pediatric patients include graft failure and chronic GVHD. MSCs from bone marrow, adipose tissue, umbilical cord, Wharton's jelly, placenta tissue, and decidua have been used, but the optimal clinical stromal cell source has not been compared in clinical trials. More experimental clinical indications using MSCs, such as sepsis, acute respiratory distress syndrome, hemorrhages, pneumo-mediastinum, and neuroinflammation have primarily been explored in animal models or adult HCT patients. MSCs have almost no if any side-effects. In this pilot study we report the outcome of six children treated with decidua stromal cells (DSCs) for steroid refractory acute GVHD. At 6 months, complete response was seen in four patients and partial response in two patients. One child with high-risk ALL died from relapse and a boy with sickle cell disease died from a cerebral hemorrhage. Five-year survival was 67% and all survivors showed a Lansky score of 100%. To conclude, MSCs from various organs are well-tolerated and have shown an encouraging outcome for acute GVHD in pediatric patients.

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Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: An updated systematic review and meta-analysis

Cited by 164 publications

References 64 publications

Emerging trends in COVID-19 treatment: learning from inflammatory conditions associated with cellular therapies

Emerging trends in COVID-19 treatment: learning from inflammatory conditions associated with cellular therapies

Human umbilical cord-derived mesenchymal stem cell therapy in patients with COVID-19: a phase 1 clinical trial

Mesenchymal Stromal Cells in Pediatric Hematopoietic Cell Transplantation a Review and a Pilot Study in Children Treated With Decidua Stromal Cells for Acute Graft-versus-Host Disease

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