Bone Marrow-Derived Mesenchymal Stem Cell-Laden Nanocomposite Scaffolds Enhance Bone Regeneration in Rabbit Critical-Size Segmental Bone Defect Model.

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.

Synergistic Hepatoprotective Effects of Mesenchymal Stem Cells and Platelet-Rich Plasma in a Rat Model of Bile Duct Ligation-Induced Liver Cirrhosis.

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.

Thermoresponsive and Injectable Pluronic F127 Hydrogel for Loading Adipose-Derived Mesenchymal Stem Cells.

BACKGROUND: Stem cell-based therapies display immense potential in regenerative medicine, highlighting the crucial significance of devising efficient delivery methods. This study centers on a pioneering approach that utilizes Pluronic F127 (PF127) as a thermoresponsive and injectable hydrogel designed for the encapsulation of adipose-derived mesenchymal stem cells (AdMSCs). METHODS: The degradation profile, gelation time, and microstructure of the PF127 hydrogel were thoroughly examined. AdMSCs were isolated, expanded, and characterized based on their multi-lineage differentiation potential. AdMSCs from the third passage were specifically employed for encapsulation within the PF127 hydrogel. Subsequently, the cytotoxicity of the AdMSC-loaded PF127 hydrogel was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and apoptosis assays. RESULTS: Characterized by scanning electron microscopy (SEM), the PF127 hydrogel exhibited a porous structure, indicating its suitability for accommodating AdMSCs and facilitating wound healing. The PF127 hydrogel demonstrated reversible phase transitions, rendering it suitable for in vivo applications. Studies on the gelation time of PF127 hydrogel unveiled a concentration-dependent decrease in gelation time, offering adaptability for diverse medical applications. Analysis of the degradation profile showcased a seven-day degradation period, leading to the decision for weekly topical applications. Cytotoxicity assessments confirmed that AdMSCs loaded into the PF127 hydrogel maintained heightened metabolic activity for up to one week, affirming the safety and appropriateness of the PF127 hydrogel for encapsulating cellular therapeutics. Furthermore, cell apoptosis assays consistently indicated low rates of apoptosis, emphasizing the viability and robust health of AdMSCs when delivered within the hydrogel. CONCLUSIONS: These findings underscore the vast potential of PF127 hydrogel as a versatile and biocompatible delivery system for AdMSCs in the realm of regenerative medicine. Boasting adjustable gelation properties and a remarkable capacity for cell encapsulation, this pioneering delivery system presents a promising path for applications in tissue engineering and wound healing. Ultimately, these advancements propel and elevate the landscape of regenerative medicine.