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1.
J Funct Biomater ; 15(3)2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38535259

RESUMO

Bone regeneration poses a significant challenge in the field of tissue engineering, prompting ongoing research to explore innovative strategies for effective bone healing. The integration of stem cells and nanomaterial scaffolds has emerged as a promising approach, offering the potential to enhance regenerative outcomes. This study focuses on the application of a stem cell-laden nanomaterial scaffold designed for bone regeneration in rabbits. The in vivo study was conducted on thirty-six healthy skeletally mature New Zealand white rabbits that were randomly allocated into six groups. Group A was considered the control, wherein a 15 mm critical-sized defect was created and left as such without any treatment. In group B, this defect was filled with a polycaprolactone-hydroxyapatite (PCL + HAP) scaffold, whereas in group C, a PCL + HAP-carboxylated multiwalled carbon nanotube (PCL + HAP + MWCNT-COOH) scaffold was used. In group D, a PCL + HAP + MWCNT-COOH scaffold was used with local injection of bone morphogenetic protein-2 (BMP-2) on postoperative days 30, 45, and 60. The rabbit bone marrow-derived mesenchymal stem cells (rBMSCs) were seeded onto the PCL + HAP + MWCNT-COOH scaffold by the centrifugal method. In group E, an rBMSC-seeded PCL + HAP + MWCNT-COOH scaffold was used along with the local injection of rBMSC on postoperative days 7, 14, and 21. For group F, in addition to the treatment given to group E, BMP-2 was administered locally on postoperative days 30, 45, and 60. Gross observations, radiological observation, scanning electron microscopic assessment, and histological evaluation study showed that group F displayed the best healing properties, followed by group E, group D, group C, and B. Group A showed no healing with ends blunting minimal fibrous tissue. Incorporating growth factor BMP-2 in tissue-engineered rBMSC-loaded nanocomposite PCL + HAP + MWCNT-COOH construct can augment the osteoinductive and osteoconductive properties, thereby enhancing the healing in a critical-sized bone defect. This novel stem cell composite could prove worthy in the treatment of non-union and delayed union fractures in the near future.

2.
Cells ; 13(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38474368

RESUMO

Liver cirrhosis poses a global health challenge marked by significant prevalence and mortality. Current therapeutic options are limited by high costs and immune-mediated rejection, necessitating the exploration of innovative strategies to enhance hepatic self-rehabilitation, and counteract the underlying pathological mechanisms. We evaluated the hepatoprotective activity of rat adipose-derived mesenchymal stem cells (ADMSCs) in combination with platelet-rich plasma (PRP) and recombinant human hepatocyte growth factor (rh-HGF) on a rat model of liver fibrosis/cirrhosis induced by bile duct ligation (BDL). Treatment with PRP or rh-HGF alone did not yield significant hepatoprotection in the BDL-induced liver cirrhosis model. However, ADMSC transplantation alone exhibited the potential to alleviate impaired liver conditions. The combination of PRP and rh-HGF demonstrated superior ameliorative effects compared to either treatment alone. Notably, the combination of ADMSC + PRP or ADMSC + rh-HGF significantly enhanced hepatoprotective capacity compared to individual or combined PRP and rh-HGF therapies. Injection of ADMSC via the tail vein reduced inflammation, hepatocyte damage, and collagen deposition, improving overall liver function. This improvement was more pronounced when ADMSC was administered with PRP and rh-HGF versus monotherapy. Our study concludes that ADMSCs exert antifibrotic effects by inhibiting hepatic stellate cell proliferation, collagen synthesis, and inducing apoptosis. ADMSCs also demonstrate immune-modulatory effects and transdifferentiate into hepatic progenitor cells, secreting trophic factors, cytokines, and chemokines that promote impaired liver regeneration. The observed arrest in liver fibrosis progression highlights the potential therapeutic impact of these interventions.


Assuntos
Células-Tronco Mesenquimais , Plasma Rico em Plaquetas , Ratos , Humanos , Animais , Cirrose Hepática/metabolismo , Fibrose , Ductos Biliares/metabolismo , Células-Tronco Mesenquimais/metabolismo , Colágeno/metabolismo , Plasma Rico em Plaquetas/metabolismo
3.
Cell Physiol Biochem ; 57(6): 452-477, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37978922

RESUMO

BACKGROUND/AIMS: All body functions are activated, synchronized and controlled by a substantial, complex network, the nervous system. Upon injury, pathophysiology of the nerve injury proceeds through different paths. The axon may undergo a degenerative retraction from the site of injury for a short distance unless the injury is near to the cell body, in which case it continues to the soma and undergoes retrograde neuronal degeneration. Otherwise, the distal section suffers from Wallerian degeneration, which is marked by axonal swelling, spheroids, and cytoskeleton degeneration. The objective of the study was to evaluate the potential of mesenchymal stem cell laden neural scaffold and insulin-like growth factor I (IGF-I) in nerve regeneration following sciatic nerve injury in a rat model. METHODS: The animals were anaesthetized and a cranio-lateral incision over left thigh was made. Sciatic nerve was exposed and crush injury was introduced for 90 seconds using haemostat at second locking position. The muscle and skin were sutured in routine fashion and thus the rat model of sciatic crush injury was prepared. The animal models were equally distributed into 5 different groups namely A, B, C, D and E and treated with phosphate buffer saline (PBS), carbon nanotubes based neural scaffold only, scaffold with IGF-I, stem cell laden scaffold and stem cell laden scaffold with IGF-I respectively. In vitro scaffold testing was performed. The nerve regeneration was assessed based on physico-neuronal, biochemical, histopathological examination, and relative expression of NRP-1, NRP-2 and GAP-43 and scanning electron microscopy. RESULTS: Sciatic nerve injury model with crush injury produced for 90 seconds was standardized and successfully used in this study. All the biochemical parameters were in normal range in all the groups indicating no scaffold related changes. Physico-neuronal, histopathological, relative gene expression and scanning electron microscopy observations revealed appreciable nerve regeneration in groups E and D, followed by C and B. Restricted to no regeneration was observed in group A. CONCLUSION: Carbon nanotubes based scaffold provided electro-conductivity for proper neuronal regeneration while rat bone marrow-derived mesenchymal stem cells were found to induce axonal sprouting, cellular transformation; whereas IGF-I induced stem cell differentiation, myelin synthesis, angiogenesis and muscle differentiation.


Assuntos
Lesões por Esmagamento , Células-Tronco Mesenquimais , Nanotubos de Carbono , Neuropatia Ciática , Ratos , Animais , Ratos Wistar , Fator de Crescimento Insulin-Like I/farmacologia , Fator de Crescimento Insulin-Like I/uso terapêutico , Neuropatia Ciática/tratamento farmacológico , Neuropatia Ciática/patologia , Nervo Isquiático/lesões , Regeneração Nervosa/fisiologia , Lesões por Esmagamento/tratamento farmacológico , Lesões por Esmagamento/patologia , Células-Tronco Mesenquimais/patologia , Colágeno
4.
Cell Tissue Bank ; 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37542003

RESUMO

Biomaterials capable of managing wounds should have essential features like providing a natural microenvironment for wound healing and as support material for stimulating tissue growth. Eggshell membrane (ESM) is a highly produced global waste due to increased egg consumption. The unique and fascinating properties of ESM allow their potential application in tissue regeneration. The wound healing capacity of bone marrow-derived mesenchymal stem cells (BM-MSCs), ESM, and their combination in rabbits with full-thickness skin defect (2 × 2 cm2) was evaluated. Twenty-five clinically healthy New Zealand White rabbits were divided into five groups of five animals each, with group A receiving no treatment (control group), group B receiving only fibrin glue (FG), group C receiving FG and ESM as a dressing, group D receiving FG and BM-MSCs, and group E receiving a combination of FG, ESM, and BM-MSCs. Wound healing was assessed using clinical, macroscopical, photographic, histological, histochemical, hematological, and biochemical analysis. Macroscopic examination of wounds revealed that healing was exceptional in group E, followed by groups D and C, compared to the control group. Histopathological findings revealed improved quality and a faster rate of healing in group E compared to groups A and B. In addition, healing in group B treated with topical FG alone was nearly identical to that in control group A. However, groups C and D showed improved and faster recovery than control groups A and B. The macroscopic, photographic, histological, and histochemical evaluations revealed that the combined use of BM-MSCs, ESM, and FG had superior and faster healing than the other groups.

5.
Cell Physiol Biochem ; 55(6): 739-760, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34816679

RESUMO

BACKGROUND/AIMS: Liver is considered as the vital organ in the body as it performs various essential functions. Following an injury to the liver, the repair process even though initially beneficial becomes pathogenic when it is not controlled appropriately. Extensive accumulation of extracellular matrix (ECM) components can ultimately lead to cirrhosis and liver failure. Thus, the ideal strategy to treat a liver injury is to generate new hepatocytes replacing damaged cells without causing excessive ECM deposition. The objective of this study was to evaluate the potential of mesenchymal stem cells, conditioned media and murine epidermal growth factor (m-EGF) in liver regeneration following partial hepatectomy in a rat model. METHODS: The animals were anaesthetized and a midline laparotomy was done. The liver was exposed and the left lateral and median lobes were ligated and resected out (about 65-70% of total liver mass). The muscles and skin were sutured in routine fashion and thus the rat model of partial hepatectomy was prepared. The animal models were equally distributed into 4 different groups namely A, B, C and D and treated with PBS, conditioned media, mesenchymal stem cells and epidermal growth factor respectively. The liver regeneration was assessed based on clinical, haemato-biochemical, colour imaging, histopathological and immune-histochemical parameters. RESULTS: Partial hepatectomy model with surgical removal of 65-70% liver lobe was standardized and successfully used in this study. Alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), bilirubin, transaminases were significantly higher (P<0.05) in group A indicating that the liver damage was not restored properly. Colour digital imaging, histopathological and immune-histochemistry observations revealed that a better liver regeneration was observed in groups C and D, followed by groups B and A. Regeneration coefficient calculated based on liver weight was higher in groups C and D as compared to group A. CONCLUSION: Rat bone marrow-derived mesenchymal stem cells were found to induce hepatocytes proliferation; whereas EGF induced more angiogenesis. Conditioned media was not as effective as stem cells and EGF in liver tissue repair.


Assuntos
Hepatectomia , Regeneração Hepática/efeitos dos fármacos , Fígado/metabolismo , Células-Tronco Mesenquimais/metabolismo , Animais , Meios de Cultivo Condicionados/farmacologia , Feminino , Fígado/cirurgia , Masculino , Ratos , Ratos Wistar
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