Tissue repair strategies: What we have learned from COVID-19 in the application of MSCs therapy

Li, Yiran E; Ajoolabady, Amir; Dhanasekaran, Muralikrishnan; Ren, Jun

doi:10.1016/j.phrs.2022.106334

Cited by 4 publications

(5 citation statements)

References 116 publications

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“…Notably, MSC-derived exosomes (MSC-Exo) are emerging as a safe and effective treatment strategy for COVID-19 according to the present results of epidemiological studies [98][99][100][101]. Previous publications have also concluded that MSC-Exo is a promising cell-free therapy for COVID-19 patients [46,102]. MSC-Exo exerts the capacity to pass the blood-brain barrier and has multiple advantages including less immunogenicity, high stability, ease of storage etc.…”

Section: Discussionmentioning

confidence: 99%

“…MSC-Exo exerts the capacity to pass the blood-brain barrier and has multiple advantages including less immunogenicity, high stability, ease of storage etc. [46,103,104] Recently, nonrandomized open-label cohort research demonstrated that MSC-Exo therapy promoted immunity function and reduced cytokine storm in COVID-19 patients. In addition, the patient's treatment experience was improved significantly after the MSC-secretome was inhaled by COVID-19 patients [105].…”

Section: Discussionmentioning

confidence: 99%

“…Some previous studies have demonstrated the efficacy and safety of MSCs in the treatment of COVID-19 or ARDS. However, potential future directions such as the optimal cell type, cell dose, and route of infusion still need to be further elaborated [46][47][48][49]. Unfortunately, few of these analyses had specifically focused on the effects of different cell types and routes of transplantation in MSC treatment upon given randomized controlled trials (RCTs).…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of mesenchymal stem cells therapy in COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials

Lu,

Yan,

Tang

et al. 2024

J Transl Med

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Background The coronavirus disease 2019 (COVID-19) has become a serious public health issue. In COVID-19 patients, the elevated levels of inflammatory cytokines lead to the manifestation of COVID-19 symptoms, such as lung tissue edema, lung diffusion dysfunction, acute respiratory distress syndrome (ARDS), secondary infection, and ultimately mortality. Mesenchymal stem cells (MSCs) exhibit anti-inflammatory and immunomodulatory properties, thus providing a potential treatment option for COVID-19. The number of clinical trials of MSCs for COVID-19 has been rising. However, the treatment protocols and therapeutic effects of MSCs for COVID-19 patients are inconsistent. This meta-analysis was performed to systematically determine the safety and efficacy of MSC infusion in COVID-19 patients. Methods We conducted a comprehensive literature search from PubMed/Medline, Web of Science, EMBASE, and Cochrane Library up to 22 November 2023 to screen for eligible randomized controlled trials. Inclusion and exclusion criteria for searched literature were formulated according to the PICOS principle, followed by the use of literature quality assessment tools to assess the risk of bias. Finally, outcome measurements including therapeutic efficacy, clinical symptoms, and adverse events of each study were extracted for statistical analysis. Results A total of 14 randomized controlled trials were collected. The results of enrolled studies demonstrated that patients with COVID-19 pneumonia who received MSC inoculation showed a decreased mortality compared with counterparts who received conventional treatment (RR: 0.76; 95% CI [0.60, 0.96]; p = 0.02). Reciprocally, MSC inoculation improved the clinical symptoms in patients (RR: 1.28; 95% CI [1.06, 1.55]; p = 0.009). In terms of immune biomarkers, MSC treatment inhibited inflammation responses in COVID-19 patients, as was indicated by the decreased levels of CRP and IL-6. Importantly, our results showed that no significant differences in the incidence of adverse reactions or serious adverse events were monitored in patients after MSC inoculation. Conclusion This meta-analysis demonstrated that MSC inoculation is effective and safe in the treatment of patients with COVID-19 pneumonia. Without increasing the incidence of adverse events or serious adverse events, MSC treatment decreased patient mortality and inflammatory levels and improved the clinical symptoms in COVID-19 patients. However, large-cohort randomized controlled trials with expanded numbers of patients are required to further confirm our results.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of mesenchymal stem cells therapy in COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials

Lu,

Yan,

Tang

et al. 2024

J Transl Med

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“…40 The main sources of MSCs are bone marrow, adipose tissues, umbilical cord, and placental tissues. MSCs-based cell therapy has seen increased attention as a possible option to treat a number of diseases such as liver fibrosis, 41 COVID-19, 42 and ischemic heart diseases. 43 Of note, MSCs have functions such as angiogenesis, antioxidant effects, metabolic regulation, and insulin resistance, 44 which are closely related to the progression of DN.…”

Section: Discussionmentioning

confidence: 99%

Marrow mesenchymal stem cell mediates diabetic nephropathy progression via modulation of Smad2/3/WTAP/m6A/ENO1 axis

Bai,

Huang,

Fan

et al. 2024

The FASEB Journal

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Diabetic nephropathy (DN) is one of the common microvascular complications in diabetic patients. Marrow mesenchymal stem cells (MSCs) have attracted attention in DN therapy but the underlying mechanism remains unclear. Here, we show that MSC administration alleviates high glucose (HG)‐induced human kidney tubular epithelial cell (HK‐2 cell) injury and ameliorates renal injury in DN mice. We identify that Smad2/3 is responsible for MSCs‐regulated DN progression. The activity of Smad2/3 was predominantly upregulated in HG‐induced HK‐2 cell and DN mice and suppressed with MSC administration. Activation of Smad2/3 via transforming growth factor‐β1 (TGF‐β1) administration abrogates the protective effect of MSCs on HG‐induced HK‐2 cell injury and renal injury of DN mice. Smad2/3 has been reported to interact with methyltransferase of N6‐methyladenosine (m6A) complex and we found a methyltransferase, Wilms' tumor 1‐associating protein (WTAP), is involved in MSCs‐Smad2/3‐regulated DN development. Moreover, WTAP overexpression abrogates the improvement of MSCs on HG‐induced HK‐2 cell injury and renal injury of DN mice. Subsequently, α‐enolase (ENO1) is the downstream target of WTAP‐mediated m6A modification and contributes to the MSCs‐mediated regulation. Collectively, these findings reveal a molecular mechanism in DN progression and indicate that Smad2/3/WTAP/ENO1 may present a target for MSCs‐mediated DN therapy.

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“…Mesenchymal stem cells (MSCs) are multipotent stem cells with self-renewal capability, multidirectional differentiation potential, and paracrine regulation [ 7 ]. Due to their easy isolation, in vitro expansion, and multipotent stemness, MSCs have been acknowledged as an important source of stem cells in the field of regenerative medicine, including tissue repair [ 8 , 9 ]. In addition to MSCs in bone marrow, MSCs are also present in adipose, muscle, umbilical cord, several organs, and other tissues.…”

Section: Introductionmentioning

confidence: 99%

Stem cell-derived exosomes: emerging therapeutic opportunities for wound healing

Zhou¹,

Zhang²,

Yang³

et al. 2023

Stem Cell Res Ther

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Wound healing is a dynamic and highly sequential process involving a series of overlapping spatial and temporal phases, including hemostasis, inflammation, proliferation, and tissue remodeling. Mesenchymal stem cells (MSCs) are multipotent stem cells with self-renewal, multidirectional differentiation potential, and paracrine regulation. Exosomes are subcellular vesicular components 30–150 nm in size and are novel carriers of intercellular communication in regulating the biological behaviors of skin cells. Compared to MSCs, MSC-derived exosomes (MSC-exos) possess lower immunogenicity, easy storage, and highly effective biological activity. MSC-exos, mainly derived from adipose-derived stem cells (ADSCs), bone marrow-derived MSCs (BMSCs), human umbilical cord MSCs (hUC-MSCs), and other stem cell types, play a role in shaping the activity of fibroblasts, keratinocytes, immune cells, and endothelial cells in diabetic wounds, inflammatory wound repair, and even wound-related keloid formation. Therefore, this study focuses on the specific roles and mechanisms of different MSC-exos in wound healing, as well as the current limitations and various perspectives. Deciphering the biological properties of MSC-exos is crucial to providing a promising cell-free therapeutic tool for wound healing and cutaneous regeneration. Graphical Abstract

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Tissue repair strategies: What we have learned from COVID-19 in the application of MSCs therapy

Cited by 4 publications

References 116 publications

Efficacy and safety of mesenchymal stem cells therapy in COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials

Efficacy and safety of mesenchymal stem cells therapy in COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials

Marrow mesenchymal stem cell mediates diabetic nephropathy progression via modulation of Smad2/3/WTAP/m6A/ENO1 axis

Stem cell-derived exosomes: emerging therapeutic opportunities for wound healing

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