Navegando por Palavras-chave "Regenerative medicine"
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- ItemAcesso aberto (Open Access)Immunomodulatory and neuroprotective effect of cryopreserved allogeneic mesenchymal stem cells on spinal cord injury in rats(Funpec-Editora, 2017) Rosado, Isabel Rodrigues; Carvalho, Pablo Herthel de; Alves, Endrigo Gabellini Leonel; Tagushi, Tatiane Malagoli; Carvalho, Juliana Lott; Silva, Juneo de Freitas; Lavor, Mário Sergio Lima de; Oliveira, Karen Maciel de [UNIFESP]; Serakides, Rogéria; Goes, Alfredo Miranda de; Melo, Eliane Gonçalves deThis study aimed to evaluate the immunomodulatory and neuroprotective effects of allogeneic and cryopreserved mesenchymal stem cells (MSCs) on spinal cord injury. A total of 120 rats were distributed into the following groups: negative control (NC) - without injury, positive control (PC) - with injury without treatment, and group treated with MSC (GMSC) - with injury and treated. Motor function was evaluated by the BBB test at 24, 48, and 72 h and at 8 and 21 postoperative days. Spinal cords were evaluated by histopathology and immunohistochemistry to determine the expression of CD68, NeuN, and GFAP. IL-10, TNF-alpha, IL-1 beta, TGF-beta, BDNF, GDNF, and VEGF expression was quantified by RT-PCR. The GMSC presented higher scores for motor function at 72 h and 8 and 21 days after injury, lower expression of CD68 at 8 days, and lower expression of GFAP at 21 days compared to the PC. In addition, higher expression of NeuN and lower degeneration of the white matter occurred at 21 days. The GMSC also showed higher expression of IL-10 24 h after injury, GDNF at 48 h and 8 days, and VEGF at 21 days. Moreover, lower expression of TNF-alpha was observed at 8 and 21 days and TGF-beta at 24 h and 21 days. There were no differences in the expression of IL-1 beta and BDNF between the GMSC and PC. Thus, cryopreserved MSCs promote immunomodulatory and neuroprotective effects in rats with spinal cord injury by increasing IL-10, GDNF, and VEGF expression and reducing TNF-alpha and TGF-beta expression.
- ItemSomente MetadadadosInjectable alginate hydrogel for enhanced spatiotemporal control of lentivector delivery in murine skeletal muscle(Elsevier Science Bv, 2016) Stilhano, Roberta Sessa [UNIFESP]; Madrigal, Justin L.; Wong, Kevin; Williams, Priscilla A.; Martin, Priscila Keiko Matsumoto [UNIFESP]; Yamaguchi, Fabio Seiji Mazzi; Samoto, Vivian Yochiko [UNIFESP]; Han, Sang Won [UNIFESP]; Silva, Eduardo AlexandreHydrogels are an especially appealing class of biomaterials for gene delivery vehicles as they can be introduced into the body with minimally invasive procedures and are often applied in tissue engineering and regenerative medicine strategies. In this study, we show for the first time the use of an injectable alginate hydrogel for controlled delivery of lentivectors in the skeletal muscle of murine hindlimb. We propose to alter the release rates of lentivectors through manipulation of the molecular weight distribution of alginate hydrogels. The release of lentivector was tested using two different ratios of low and high molecular weight (MW) alginate polymers (75/25 and 25/75 low/high MW). The interdependency of lentivector release rate and alginate degradation rate was assessed in vitro. Lentivector-loaded hydrogels maintained transduction potential for up to one week in vitro as demonstrated by the continual transduction of HEK-293T cells. Injection of lentivector-loaded hydrogel in vivo led to a sustained level of transgene expression for more than two months while minimizing the copies of lentivirus genome inserted into the genome of murine skeletal muscle cells. This strategy of spatiotemporal control of lentivector delivery from alginate hydrogels may provide a versatile tool to combine gene therapy and biomaterials for applications in regenerative medicine. (C) 2016 Elsevier B.V. All rights reserved.