Mesenchymal Stem Cells Enhance Nerve Regeneration in a Rat Sciatic Nerve Repair and Hindlimb Transplant Model

Abstract

This study investigates the efficacy of local and intravenous mesenchymal stem cell (MSC) administration to augment neuroregeneration in both a sciatic nerve cut-and-repair and rat hindlimb transplant model. Bone marrow-derived MSCs were harvested and purified from Brown-Norway (BN) rats. Sciatic nerve transections and repairs were performed in three groups of Lewis (LEW) rats: negative controls (n = 4), local MSCs (epineural) injection (n = 4), and systemic MSCs (intravenous) injection (n = 4). Syngeneic (LEW-LEW) (n = 4) and allogeneic (BN-LEW) (n = 4) hindlimb transplants were performed and assessed for neuroregeneration after local or systemic MSC treatment. Rats undergoing sciatic nerve cut-and-repair and treated with either local or systemic injection of MSCs had significant improvement in the speed of recovery of compound muscle action potential amplitudes and axon counts when compared with negative controls. Similarly, rats undergoing allogeneic hindlimb transplants treated with local injection of MSCs exhibited significantly increased axon counts. Similarly, systemic MSC treatment resulted in improved nerve regeneration following allogeneic hindlimb transplants. Systemic administration had a more pronounced effect on electromotor recovery while local injection was more effective at increasing fiber counts, suggesting different targets of action. Local and systemic MSC injections significantly improve the pace and degree of nerve regeneration after nerve injury and hindlimb transplantation.

Delivery of adipose‐derived stem cells in poloxamer hydrogel improves peripheral nerve regeneration

“…A multimodal approach in evaluation of this therapeutic modality resulted in a positive effect on axonal growth and the activation of muscle regenerative transcriptional programming and, additionally, provided some potential insights into the role of immunomodulation in peripheral nerve regeneration. Previous work has shown improved outcomes with transplantation of mesenchymal origin stem cells, including a previous study evaluating the use specifically of ASCs . ASCs have several properties that make them an attractive therapeutic adjuvant for repair of peripheral nerve injury, including the secretion of relevant growth factors and cytokines, immunomodulatory effects, and clinical translatability …”

“…The group treated with ASCs delivered in PBS had the second smallest number of DAPI + objects; it may be that a decreased number of surviving ASCs with this delivery method leads to a reduced efficacy of the hypothesized immunomodulatory effects of these cells. Increasing interest in the role of immunomodulation in peripheral nerve regeneration has led to a number of studies demonstrating the importance of “fine‐tuning” this response.…”

Epineural adipose‐derived stem cell injection in a sciatic rodent model

“…Alternative strategies and methods can be applied to enhance peripheral nerve regeneration using ASCs, for example, hydrogels as scaffolds and delivery systems, or intravenously, spreading throughout the body and get to their target organs by a homing response to the injured neurological tissue (Carballo‐Molina & Velasco, ; Cooney et al., ; Marconi et al., ; Zack‐Williams, Butler, & Kalaskar, ). In a recent study by Sowa et al., ASCs and SCs were transplanted with gelatin hydrogel tubes at the artificially blunted sciatic nerve lesion in mice.…”

Comunicação exossomal na transdiferenciação de células-tronco em cocultivo com células neuronais

“…Um outro aspecto que deve ser considerado para caracterização das ADSC e outras fontes de células-tronco mesenquimais é a capacidade de diferenciação em linhagens celulares mesodérmica como osteoblastos (HANADA et al, 1997), condrócitos (TECHNAU et al, 2011) e adipócitos (DU et al, 2016GIMBLE;GUILAK, 2003;), assim como linhagens celulares ectodérmica como neurônios (ABDANIPOUR; TIRAIHI, 2012;DHANASEKARAN et al, 2013;FRANCO LAMBERT et al, 2009;HUANG et al, 2007;KURIHARA et al, 2014), células da glia (ZAVAN et al, 2010) e células de Schwann (LIU, F. et al, 2013;WANG et al, 2017;XU et al, 2008 A aplicabilidade terapêutica é um ponto importante a ser considerado quando se trabalha com células-tronco como terapia regenerativa. No caso das ADSC já foi demonstrado por Cooney et al (2016), De Lombardo et al (2009) e Delarosa e Lombardo (2010) sua capacidade de modulação e atuação no processo de regeneração em lesões de nervo periférico. A regeneração celular induzida pelas ADSC, deve-se ao fato dessas células serem imunoprivilegiadas, por terem menor expressão de MHC I, fato este, que as tornam uma valiosa fonte de células-tronco adultas para a terapia regenerativa do sistema nervoso periférico (BAGLIONI et al, 2009;CHURCH et al, 2014;GIMBLE;GUILAK, 2003;LOCKE;WINDSOR;DUNBAR, 2009;WANKHADE et al, 2016).…”

“…A principal consequência da lesões de nervo periférico (PNI -sigla em inglês para peripheral nerve injury) é a perda definitiva da função do membro ou local afetado, sendo que muitas vezes o uso de transplante de nervo do próprio paciente, assim como a utilização de biomateriais em conjunto ou não com células-tronco, se tornam uma alternativa na busca da regeneração e retorno da função (BUENO et al, 2017;COONEY et al, 2016;GÄRTNER et al, 2014;HEI et al, 2017;MARCONI et al, 2012;ZHANG, T. et al, 2014;WANG et al, 2010;WANG et al, 2017).…”