A novel therapeutic combination of mesenchymal stem cells and stigmasterol to attenuate osteoarthritis in rodent model system— a proof of concept study

Sampath, Samuel Joshua Pragasam; Kotikalapudi, Nagasuryaprasad; Venkatesan, Vijayalakshmi

doi:10.21037/sci-2020-048

Cited by 15 publications

(8 citation statements)

References 17 publications

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“…In order to develop a novel therapeutic approach to alleviate OA, Sampath et al [ 45 ] conducted an in vivo study to examine the effect of the combination of mesenchymal stem cells (MSCs) and stigmasterol in a monosodium-iodoacetate (MIA)-induced experimental OA in rats. The results demonstrated that the combination treatment led to consistent regeneration/repair of eroded cartilage in the femoral condyles and also in the trochlear groove, highlighting the importance of combined treatment over individual therapies in rats with OA.…”

Section: Anti-osteoarthritis Effectsmentioning

confidence: 99%

“…Previous studies found that stigmasterol relieved cartilage degradation in rodent models of osteoarthritis [ 44 ]. When combined with mesenchymal stem cell secretome, stigmasterol reduces inflammation and leads to constant regeneration/repair of eroded cartilage [ 45 , 46 ]. This phytosterol could be considered in new therapeutic designs since it has anti-inflammatory and analgesic properties that can overcome osteoarthritis effects [ 47 ].…”

Section: Introductionmentioning

confidence: 99%

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Health Benefits and Pharmacological Properties of Stigmasterol

et al. 2022

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Stigmasterol is an unsaturated phytosterol belonging to the class of tetracyclic triterpenes. It is one of the most common plant sterols, found in a variety of natural sources, including vegetable fats or oils from many plants. Currently, stigmasterol has been examined via in vitro and in vivo assays and molecular docking for its various biological activities on different metabolic disorders. The findings indicate potent pharmacological effects such as anticancer, anti-osteoarthritis, anti-inflammatory, anti-diabetic, immunomodulatory, antiparasitic, antifungal, antibacterial, antioxidant, and neuroprotective properties. Indeed, stigmasterol from plants and algae is a promising molecule in the development of drugs for cancer therapy by triggering intracellular signaling pathways in numerous cancers. It acts on the Akt/mTOR and JAK/STAT pathways in ovarian and gastric cancers. In addition, stigmasterol markedly disrupted angiogenesis in human cholangiocarcinoma by tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor receptor-2 (VEGFR-2) signaling down-regulation. The association of stigmasterol and sorafenib promoted caspase-3 activity and down-regulated levels of the anti-apoptotic protein Bcl-2 in breast cancer. Antioxidant activities ensuring lipid peroxidation and DNA damage lowering conferred to stigmasterol chemoprotective activities in skin cancer. Reactive oxygen species (ROS) regulation also contributes to the neuroprotective effects of stigmasterol, as well as dopamine depletion and acetylcholinesterase inhibition. The anti-inflammatory properties of phytosterols involve the production of anti-inflammatory cytokines, the decrease in inflammatory mediator release, and the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Stigmasterol exerts anti-diabetic effects by reducing fasting glucose, serum insulin levels, and oral glucose tolerance. Other findings showed the antiparasitic activities of this molecule against certain strains of parasites such as Trypanosoma congolense (in vivo) and on promastigotes and amastigotes of the Leishmania major (in vitro). Some stigmasterol-rich plants were able to inhibit Candida albicans, virusei, and tropicalis at low doses. Accordingly, this review outlines key insights into the pharmacological abilities of stigmasterol and the specific mechanisms of action underlying some of these effects. Additionally, further investigation regarding pharmacodynamics, pharmacokinetics, and toxicology is recommended.

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Section: Anti-osteoarthritis Effectsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Health Benefits and Pharmacological Properties of Stigmasterol

et al. 2022

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“…In that sense, 8 more animals were included in this study and were subjected to HBO treatment during 14 days after OA induction. Animals from this group were sacrificed after 28 days of OA induction (HBO+ADS 28day group) in order to compare cartilage damage to rats from HBO+ADS 21day group [ 35 , 36 ].…”

Section: Methodsmentioning

confidence: 99%

Effects of Combined Allogenic Adipose Stem Cells and Hyperbaric Oxygenation Treatment on Pathogenesis of Osteoarthritis in Knee Joint Induced by Monoiodoacetate

Juskovic

Turnic

Ljujić

et al. 2022

IJMS

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The beneficial effects of HBO in inflammatory processes make it an attractive type of treatment for chronic arthritis. In addition, the effects of combination therapy based on adipose stem cells and HBO on OA progression have not been fully investigated. The current study explored the efficacy of intra-articular injection of allogeneic adipose-derived mesenchymal stem cells (ADMSCs) combined with hyperbaric oxygenation treatment (HBO) in a rat osteoarthritis (OA) model. The rat OA model was induced by intra-articular injection of monoiodoacetate (MIA) and 7 days after application of MIA rats were divided into five groups: healthy control (CTRL), osteoarthritis (OA), ADMSCs (ADS), the HBO+ADS21day and HBO+ADS28day groups. A single dose of 1 × 106 allogeneic ADMSCs suspended in sterile saline was injected into the knee joint alone or in combination with HBO treatment. Rats were sacrificed at 3 or 4 weeks after MIA injection. Treatment outcomes were evaluated by radiographic, morphological and histological analysis and by specific staining of articular cartilage. We also measured the level of inflammatory and pro/antioxidative markers. We confirmed that combined treatment of ADMSCs and HBO significantly improved the regeneration of cartilage in the knee joint. Rtg score of knee joint damage was significantly decreased in the HBO+ADS21day and HBO+ADS28day groups compared to the OA. However, the positive effect in the HBO+ADS28day group was greater than the HBO+ADS21day group. The articular cartilage was relatively normal in the HBO+ADS28day group, but moderate degeneration was observed in the HBO+ADS21day compared to the OA group. These findings are in line with the histopathological results. A significantly lower level of O2−. was observed in the HBO+ADS28day group but a higher NO level compared to the HBO+ADS21day group. Moreover, in the HBO+ADS28day group significantly higher concentrations of IL-10 were observed but there was no significant difference in proinflammatory cytokine in serum samples. These results indicate that a single intra-articular injection of allogeneic ADMSCs combined with HBO efficiently attenuated OA progression after 28 days with greater therapeutic effect compared to alone ADMSCs or after 3 weeks of combined treatment. Combined treatment might be an effective treatment for OA in humans.

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“…Many studies postulated that higher efficacy with MSCs can be achieved with the infusion of stem cells before disease onset or during the early phase of the disease. Recently, Sampath et al [ 54 ] reported a novel therapeutic combination of placental-derived MSCs (hPMSCs) with stigmasterol, a plant-derived sterol in the monosodium-iodoacetate osteoarthritis (OA) rat model. The authors found beneficial effects on intra-articular administration of hPMSCs with stigmasterol and demonstrated accelerated cartilage repair and regeneration using computerised tomography (micro-CT) and histopathology.…”

Section: Preclinical Animal Models Of Autoimmune Diseasesmentioning

confidence: 99%

“…The authors found beneficial effects on intra-articular administration of hPMSCs with stigmasterol and demonstrated accelerated cartilage repair and regeneration using computerised tomography (micro-CT) and histopathology. This cellular therapy attenuated osteoarthritis lesions with concomitant cartilage repair and regeneration [ 54 ].…”

Section: Preclinical Animal Models Of Autoimmune Diseasesmentioning

confidence: 99%

Evaluation of the Therapeutic Potential of Mesenchymal Stem Cells (MSCs) in Preclinical Models of Autoimmune Diseases

Shandil

Dhup

Narayanan

2022

Stem Cells International

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Autoimmune diseases, chronic in nature, are generally hard to alleviate. Present long-term treatments with available drugs such as steroids, immune-suppressive drugs, or antibodies have several debilitating side effects. Therefore, new treatment options are urgently needed. Stem cells, in general, have the potential to reduce immune-mediated damage through immunomodulation and T cell regulation (T regs) by inhibiting the proliferation of dendritic cells and T and B cells and reducing inflammation through the generation of immunosuppressive biomolecules like interleukin 10 (IL-10), transforming growth factor-β (TGF-β), nitric oxide (NO), indoleamine 2,3-dioxygenase (IDO), and prostaglandin E2 (PGE2). Many stem cell-based therapeutics have been evaluated in the clinic, but the overall clinical outcomes in terms of efficacy and the longevity of therapeutic benefits seem to be variable and inconsistent with the postulated benefits. This emphasizes a greater need for building robust preclinical models and models that can better predict the clinical translation of stem cell-based therapeutics. Stem cell therapy based on MSCs having the definitive potential to regulate the immune system and control inflammation is emerging as a promising tool for the treatment of autoimmune disorders while promoting tissue regeneration. MSCs, derived from bone marrow, umbilical cord, and adipose tissue, have been shown to be highly immunomodulatory and anti-inflammatory and shown to enhance tissue repair and regeneration in preclinical models as well as in clinical settings. In this article, a review on the status of MSC-based preclinical disease models with emphasis on understanding disease mechanisms in chronic inflammatory disorders caused by exaggerated host immune response in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) was carried out. We also emphasized various factors that better predict the translation of stem cell therapeutic outcomes from preclinical disease models to human patients.

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A novel therapeutic combination of mesenchymal stem cells and stigmasterol to attenuate osteoarthritis in rodent model system— a proof of concept study

Cited by 15 publications

References 17 publications

Health Benefits and Pharmacological Properties of Stigmasterol

Health Benefits and Pharmacological Properties of Stigmasterol

Effects of Combined Allogenic Adipose Stem Cells and Hyperbaric Oxygenation Treatment on Pathogenesis of Osteoarthritis in Knee Joint Induced by Monoiodoacetate

Evaluation of the Therapeutic Potential of Mesenchymal Stem Cells (MSCs) in Preclinical Models of Autoimmune Diseases

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