Abstract:BACKGROUND
Conventional Crohn’s disease (CD) treatments are supportive rather than curative and have serious side effects. Adipose-derived mesenchymal stem cells (ADSCs) have been gradually applied to treat various diseases. The therapeutic effect and underlying mechanism of ADSCs on CD are still not clear.
AIM
To investigate the effect of ADSC administration on CD and explore the potential mechanisms.
METHODS
Wistar rats were administered wi… Show more
“…Likewise, other examinations indicated that AT-MSC administration attenuated the disease activity index (DAI) and improved the severity of colitis in a rodent CD model. Significantly, regulation of intestinal epithelial cell (IEC) proliferation, Wnt signaling pathway, and T cell immunity were suggested as the underlying mechanism of the AT-MSC-prompted therapeutic effect in the rodent CD model [ 111 ]. The crucial role of the Wnt axis has already been confirmed in murine IBD, where Roger et al showed that injection of a Wnt agonist to STAT6 (−/−) mice induced the Wnt signaling in the damaged mucosa and accelerated wound-healing in the TNBS-induced CD model [ 112 ].…”
Section: Application Of Msc Therapy In Immune-mediated Disordersmentioning
Over recent years, mesenchymal stem/stromal cells (MSCs) and their potential biomedical applications have received much attention from the global scientific community in an increasing manner. Firstly, MSCs were successfully isolated from human bone marrow (BM), but in the next steps, they were also extracted from other sources, mostly from the umbilical cord (UC) and adipose tissue (AT). The International Society for Cellular Therapy (ISCT) has suggested minimum criteria to identify and characterize MSCs as follows: plastic adherence, surface expression of CD73, D90, CD105 in the lack of expression of CD14, CD34, CD45, and human leucocyte antigen-DR (HLA-DR), and also the capability to differentiate to multiple cell types including adipocyte, chondrocyte, or osteoblast in vitro depends on culture conditions. However, these distinct properties, including self-renewability, multipotency, and easy accessibility are just one side of the coin; another side is their huge secretome which is comprised of hundreds of mediators, cytokines, and signaling molecules and can effectively modulate the inflammatory responses and control the infiltration process that finally leads to a regulated tissue repair/healing or regeneration process. MSC-mediated immunomodulation is a direct result of a harmonic synergy of MSC-released signaling molecules (i.e., mediators, cytokines, and chemokines), the reaction of immune cells and other target cells to those molecules, and also feedback in the MSC-molecule-target cell axis. These features make MSCs a respectable and eligible therapeutic candidate to be evaluated in immune-mediated disorders, such as graft versus host diseases (GVHD), multiple sclerosis (MS), Crohn’s disease (CD), and osteoarthritis (OA), and even in immune-dysregulating infectious diseases such as the novel coronavirus disease 2019 (COVID-19). This paper discussed the therapeutic applications of MSC secretome and its biomedical aspects related to immune-mediated conditions. Sources for MSC extraction, their migration and homing properties, therapeutic molecules released by MSCs, and the pathways and molecular mechanisms possibly involved in the exceptional immunoregulatory competence of MSCs were discussed. Besides, the novel discoveries and recent findings on immunomodulatory plasticity of MSCs, clinical applications, and the methods required for their use as an effective therapeutic option in patients with immune-mediated/immune-dysregulating diseases were highlighted.
“…Likewise, other examinations indicated that AT-MSC administration attenuated the disease activity index (DAI) and improved the severity of colitis in a rodent CD model. Significantly, regulation of intestinal epithelial cell (IEC) proliferation, Wnt signaling pathway, and T cell immunity were suggested as the underlying mechanism of the AT-MSC-prompted therapeutic effect in the rodent CD model [ 111 ]. The crucial role of the Wnt axis has already been confirmed in murine IBD, where Roger et al showed that injection of a Wnt agonist to STAT6 (−/−) mice induced the Wnt signaling in the damaged mucosa and accelerated wound-healing in the TNBS-induced CD model [ 112 ].…”
Section: Application Of Msc Therapy In Immune-mediated Disordersmentioning
Over recent years, mesenchymal stem/stromal cells (MSCs) and their potential biomedical applications have received much attention from the global scientific community in an increasing manner. Firstly, MSCs were successfully isolated from human bone marrow (BM), but in the next steps, they were also extracted from other sources, mostly from the umbilical cord (UC) and adipose tissue (AT). The International Society for Cellular Therapy (ISCT) has suggested minimum criteria to identify and characterize MSCs as follows: plastic adherence, surface expression of CD73, D90, CD105 in the lack of expression of CD14, CD34, CD45, and human leucocyte antigen-DR (HLA-DR), and also the capability to differentiate to multiple cell types including adipocyte, chondrocyte, or osteoblast in vitro depends on culture conditions. However, these distinct properties, including self-renewability, multipotency, and easy accessibility are just one side of the coin; another side is their huge secretome which is comprised of hundreds of mediators, cytokines, and signaling molecules and can effectively modulate the inflammatory responses and control the infiltration process that finally leads to a regulated tissue repair/healing or regeneration process. MSC-mediated immunomodulation is a direct result of a harmonic synergy of MSC-released signaling molecules (i.e., mediators, cytokines, and chemokines), the reaction of immune cells and other target cells to those molecules, and also feedback in the MSC-molecule-target cell axis. These features make MSCs a respectable and eligible therapeutic candidate to be evaluated in immune-mediated disorders, such as graft versus host diseases (GVHD), multiple sclerosis (MS), Crohn’s disease (CD), and osteoarthritis (OA), and even in immune-dysregulating infectious diseases such as the novel coronavirus disease 2019 (COVID-19). This paper discussed the therapeutic applications of MSC secretome and its biomedical aspects related to immune-mediated conditions. Sources for MSC extraction, their migration and homing properties, therapeutic molecules released by MSCs, and the pathways and molecular mechanisms possibly involved in the exceptional immunoregulatory competence of MSCs were discussed. Besides, the novel discoveries and recent findings on immunomodulatory plasticity of MSCs, clinical applications, and the methods required for their use as an effective therapeutic option in patients with immune-mediated/immune-dysregulating diseases were highlighted.
“…Of the 28 studies, 12 [ 16 , 18 – 23 , 25 , 27 , 28 , 31 , 32 ] reported DAI scores, 9 on day 1 ( n = 118 animals), 9 on day 3 ( n = 118), 11 on day 5 ( n = 134), 3 on day 7 ( n = 124), and 5 on day 9 ( n = 64). A random effects model was chosen for analysis, and the Cohen method was used to assess differences in DAI between the treatment and control groups.…”
Section: Resultsmentioning
confidence: 99%
“…The heterogeneity exhibited by the day 3 and 9 subgroups fell to moderate levels after deleting the studies of Banerjee et al [ 23 ] and Gonzalez-Rey et al [ 21 ]; and Gonzalez-Rey et al [ 21 ], respectively. The heterogeneity associated with the day 1 and 7 subgroup disappeared after excluding Kawata et al [ 32 ] and Forte et al [ 16 ]; Gao et al [ 18 ], Gonzalez-Rey et al [ 21 ] and Ji Young Lim et al [ 26 ], respectively. Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Three studies [ 18 , 41 , 43 ] ( n = 42 animals) reported rat colon lengths; we again used a random-effect model to compare colon lengths between the treatment and control groups while employing the Cohen method. Colon lengths in the experimental groups were longer than those in the control groups (SMD 1.44, 95% CI 0.04–2.84, I 2 = 71.7%, P = 0.029) (Fig.…”
Background
We explored whether stem cell therapy was effective for animal models and patients with Crohn’s disease (CD).
Methods
We searched five online databases. The relative outcomes were analyzed with the aid of GetData Graph Digitizer 2.26 and Stata 16.0 software. The SYRCLE risk of bias tool and the MINORS tool were used to assess study quality.
Results
We evaluated 46 studies including 28 animal works (n = 567) and 18 human trials (n = 360). In the animal studies, the disease activity index dramatically decreased in the mesenchymal stem cell (MSC) treatment groups compared to the control group. Rats and mice receiving MSCs exhibited longer colons [mice: standardized mean difference (SMD) 2.84, P = 0.000; rats: SMD 1.44, P = 0.029], lower histopathological scores (mice: SMD − 4.58, p = 0.000; rats: SMD − 1.41, P = 0.000) and lower myeloperoxidase levels (SMD − 6.22, P = 0.000). In clinical trials, stem cell transplantation reduced the CD activity index (SMD − 2.10, P = 0.000), the CD endoscopic index of severity (SMD − 3.40, P = 0.000) and simplified endoscopy score for CD (SMD − 1.71, P = 0.000) and improved the inflammatory bowel disease questionnaire score (SMD 1.33, P = 0.305) compared to control values. CD patients maintained high remission rates for 3–24 months after transplantation.
Conclusions
Stem cell transplantation is a valuable supplementary therapy for CD.
“…These EVs have the ability to migrate into damaged tissues, promote tissue repair, and modulate immune responses. 20 , 129 , 131 Therefore, EVs may serve as potential nanocarriers for efficient, targeted drug delivery in IBD treatment.…”
Inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis are highly debilitating. IBDs are associated with the imbalance of inflammatory mediators within the inflamed bowel. Conventional drugs for IBD treatment include anti-inflammatory medications and immune suppressants. However, they suffer from a lack of bioavailability and high dose-induced systemic side effects. Nanoparticle (NP)-derived therapy improves therapeutic efficacy and increases targeting specificity. Recent studies have shown that nanomedicines, based on bowel disease’s pathophysiology, are a fast-growing field. NPs can prolong the circulation period and reduce side effects by improving drug encapsulation and targeted delivery. Here, this review summarizes various IBD therapies with a focus on NP-derived applications, whereas their challenges and future perspectives have also been discussed.
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