Intra-articular knee implantation of autologous bone marrow–derived mesenchymal stromal cells in rheumatoid arthritis patients with knee involvement: Results of a randomized, triple-blind, placebo-controlled phase 1/2 clinical trial

Shadmanfar, Soraya; Labibzadeh, Narges; Emadedin, Mohsen; Jaroughi, Neda; Azimian, Vajiheh; Mardpour, Soura; Kakroodi, Fatemeh Abbasi; Bolurieh, Tina; Hosseini, Seyed Ebrahim; Chehrazi, Mohammad; Niknejadi, Maryam; Baharvand, Hossein; Gharibdoost, Farhad; Aghdami, Nasser

doi:10.1016/j.jcyt.2017.12.009

Cited by 80 publications

(48 citation statements)

References 32 publications

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“…A clinical trial conducted in Iran found that autologous bone marrow-derived mesenchymal stem cells ameliorated the clinical symptoms of refractory RA (Ghoryani et al, 2019). Another phase 1/2 clinical trial observed that autologous bone marrow-derived mesenchymal stromal cells increase the clinical efficacy of MTX and prednisolone and reduce their use (Shadmanfar et al, 2018). Animal experiments using relatively uniform methods have also shown that HUMSCs can be utilized to treat CIA (Cheng-Chi et al, 2012;Shin et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…The abovementioned characteristics indicate the potential of using HUMSCs to treat autoimmune diseases (ADs), and this finding has been verified (Uccelli et al, 2008). Specifically, the use of HUMSCs in RA has shown promising results in clinical trials (Shadmanfar et al, 2018;Ghoryani et al, 2019). Basic studies have also suggested that HUMSCs can alleviate collagen-induced arthritis (CIA) partly by regulating Tregs and Th17 cells (Liu et al, 2010;Tong et al, 2015;Ma et al, 2019), but further research on the molecular mechanisms and interconnections between these different mechanisms remains rare.…”

Section: Introductionmentioning

confidence: 95%

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Human Umbilical Mesenchymal Stem Cells Display Therapeutic Potential in Rheumatoid Arthritis by Regulating Interactions Between Immunity and Gut Microbiota via the Aryl Hydrocarbon Receptor

Lü

Fan

et al. 2020

Front. Cell Dev. Biol.

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Background: Rheumatoid arthritis (RA) is an autoimmune disease that may be associated with gut microbiota via the aryl hydrocarbon receptor (AhR). Human umbilical mesenchymal stem cells (HUMSCs) have therapeutic potential against RA, but the underlying mechanism has not been fully elucidated. The purpose of this study was to explore the mechanism of action of HUMSCs in rats with collagen-induced arthritis (CIA). Method: HUMSCs (1 × 10 6) were transplanted into each rat with CIA. The tissue localization of HUMSCs and the therapeutic effects in the ankles were assessed. The immune status and expression of immune-related genes and proteins in related lymphoid tissues were subsequently tested. Furthermore, the levels of immune-related factors in serum and the changes in gut microbiota in the ileum were detected, and the levels of indole and their derivatives in plasma and the levels of AhR in the ileum were evaluated. Results: HUMSCs homed to the popliteal lymph node (PLN), mesenteric lymph node (MLN), ankle cartilage, and ileum mucosa in rats with CIA. The transplantation of HUMSCs reduced the pathology scores and the degree of bone damage in the ankles. The immune status of T regulatory cells (Tregs) and T helper (Th)17 cells and the gene expression levels of interleukin (IL)-10, transforming growth factor (TGF)-β1, and IL-17A were altered in the PLN, which is the lymph tissue closest to the nidus, and the MLN, which is one of the gut-associated lymphoid tissues (GALTs). The proportion and function of B cells, Tregs, and Th17 cells were regulated in other GALTs, namely,

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Human Umbilical Mesenchymal Stem Cells Display Therapeutic Potential in Rheumatoid Arthritis by Regulating Interactions Between Immunity and Gut Microbiota via the Aryl Hydrocarbon Receptor

Lü

Fan

et al. 2020

Front. Cell Dev. Biol.

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“…BMSCs are considered to be the best stem cells for the treatment of RA when compared to UCSCs and exfoliated deciduous teeth stem cells [138]. In addition, a randomized, triple-blind trial showed the improvement of Western Ontario and McMaster Universities Arthritis Index (WOMAC), visual analog scale (VAS), time to jelling, pain-free walking distance, and standing time in 30 RA patients treated with BMSCs [139]. However, the trial failed to prolong the therapeutic effects of BMSCs beyond 12 months.…”

Section: Bmscs Involved In the Treatment Of Immune Disorder Diseasesmentioning

confidence: 99%

An Update on the Progress of Isolation, Culture, Storage, and Clinical Application of Human Bone Marrow Mesenchymal Stem/Stromal Cells

Chu

Phuong

Tien

et al. 2020

IJMS

123

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Bone marrow mesenchymal stem/stromal cells (BMSCs), which are known as multipotent cells, are widely used in the treatment of various diseases via their self-renewable, differentiation, and immunomodulatory properties. In-vitro and in-vivo studies have supported the understanding mechanisms, safety, and efficacy of BMSCs therapy in clinical applications. The number of clinical trials in phase I/II is accelerating; however, they are limited in the size of subjects, regulations, and standards for the preparation and transportation and administration of BMSCs, leading to inconsistency in the input and outcome of the therapy. Based on the International Society for Cellular Therapy guidelines, the characterization, isolation, cultivation, differentiation, and applications can be optimized and standardized, which are compliant with good manufacturing practice requirements to produce clinical-grade preparation of BMSCs. This review highlights and updates on the progress of production, as well as provides further challenges in the studies of BMSCs, for the approval of BMSCs widely in clinical application.

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“…This disease leads to cartilage and bone degradations, causing pain and stiffness and may occur in other sites including tendon sheaths and bursae. The prevalence of this disease is approximately 0.5–1% in adults aged 40–50 years and is more common among women than men [ 216 , 217 ]. Recently, MSC-based therapies have been suggested as favorable therapeutic approaches for inflammatory cartilage injuries such as RA.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells: amazing remedies for bone and cartilage defects

et al. 2020

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Skeletal disorders are among the leading debilitating factors affecting millions of people worldwide. The use of stem cells for tissue repair has raised many promises in various medical fields, including skeletal disorders. Mesenchymal stem cells (MSCs) are multipotent stromal cells with mesodermal and neural crest origin. These cells are one of the most attractive candidates in regenerative medicine, and their use could be helpful in repairing and regeneration of skeletal disorders through several mechanisms including homing, angiogenesis, differentiation, and response to inflammatory condition. The most widely studied sources of MSCs are bone marrow (BM), adipose tissue, muscle, umbilical cord (UC), umbilical cord blood (UCB), placenta (PL), Wharton’s jelly (WJ), and amniotic fluid. These cells are capable of differentiating into osteoblasts, chondrocytes, adipocytes, and myocytes in vitro. MSCs obtained from various sources have diverse capabilities of secreting many different cytokines, growth factors, and chemokines. It is believed that the salutary effects of MSCs from different sources are not alike in terms of repairing or reformation of injured skeletal tissues. Accordingly, differential identification of MSCs’ secretome enables us to make optimal choices in skeletal disorders considering various sources. This review discusses and compares the therapeutic abilities of MSCs from different sources for bone and cartilage diseases.

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Intra-articular knee implantation of autologous bone marrow–derived mesenchymal stromal cells in rheumatoid arthritis patients with knee involvement: Results of a randomized, triple-blind, placebo-controlled phase 1/2 clinical trial

Cited by 80 publications

References 32 publications

Human Umbilical Mesenchymal Stem Cells Display Therapeutic Potential in Rheumatoid Arthritis by Regulating Interactions Between Immunity and Gut Microbiota via the Aryl Hydrocarbon Receptor

Human Umbilical Mesenchymal Stem Cells Display Therapeutic Potential in Rheumatoid Arthritis by Regulating Interactions Between Immunity and Gut Microbiota via the Aryl Hydrocarbon Receptor

An Update on the Progress of Isolation, Culture, Storage, and Clinical Application of Human Bone Marrow Mesenchymal Stem/Stromal Cells

Mesenchymal stem cells: amazing remedies for bone and cartilage defects

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