Feasibility and safety of intrathecal transplantation of autologous bone marrow mesenchymal stem cells in horses

Abstract

BackgroundRecent studies have demonstrated numerous biological properties of mesenchymal stem cells and their potential application in treating complex diseases or injuries to tissues that have difficulty regenerating, such as those affecting the central and peripheral nervous system. Thus, therapies that use mesenchymal stem cells are promising because of their high capacity for self-regeneration, their low immunogenicity, and their paracrine, anti-inflammatory, immunomodulatory, anti-apoptotic and neuroprotective effects. In this context, the purpose of this study was to evaluate the feasibility and safety of intrathecal transplantation of bone marrow-derived mesenchymal stem cells in horses, for future application in the treatment of neurological diseases.ResultsDuring the neurological evaluations, no clinical signs were observed that were related to brain and/or spinal cord injury of the animals from the control group or the treated group. The hematological and cerebrospinal fluid results from day 1 and day 6 showed no significant differences (P > 0.05) between the treated group and the control group. Additionally, analysis of the expression of matrix metalloproteinase (MMP) -2 and −9 in the cerebrospinal fluid revealed only the presence of pro-MMP-2 (latent), with no significant difference (P > 0.05) between the studied groups.ConclusionsThe results of the present study support the hypothesis of the feasibility and safety of intrathecal transplantation of autologous bone marrow-derived mesenchymal stem cells, indicating that it is a promising pathway for cell delivery for the treatment of neurological disorders in horses.

Conditioned medium: a new alternative for cryopreservation of equine umbilical cord mesenchymal stem cells

“…Prior to cryopreservation, UCIM-MSCs were satisfactorily characterized with respect to morphology, plastic adherence, immunophenotypic profile, potential to differentiate into mesodermal lineages, clonicity, and chromosomal stability. These characteristics corroborate with some findings observed in other studies with UCIM-MSCs from umbilical cord (Hoynowski et al, 2007;Lange-Consiglio et al, 2011;Barberini et al, 2014), amniotic liquid (De , amniotic membrane (Lange-Consiglio et al, 2012), bone marrow (Maia et al, 2012(Maia et al, , 2015, adipose tissue (Carvalho et al, 2013b), and peripheral blood (Martinello et al, 2010;Carvalho et al, 2013a).…”

“…Although it has disadvantages mainly related to immunogenicity for clinical application purposes, FBS has an important role in the cryopreservation process by stabilizing cell membranes, protecting cells from free radicals and adjusting osmotic pressure (Marquez‐Curtis et al, ). Many studies, used FBS for cultivation (Barberini et al, ; Maia et al, ; Chang et al, ; Tang et al, ) and cryopreservation (Mambell et al, ; Martinello et al, ; Hennes et al, ; Kim et al, ; Munévar et al, ; Duan and Lopez, ; Ercolin et al, ; Irioda et al, ) possibly by its positive aspect in cell growth and benefits during freezing. However, it is important to point that for therapeutic purposes, the FBS must be washed out before cell transfer (Maia et al, ).…”

“…Although it has disadvantages mainly related to immunogenicity for clinical application purposes, FBS has an important role in the cryopreservation process by stabilizing cell membranes, protecting cells from free radicals and adjusting osmotic pressure (Marquez-Curtis et al, 2015). Many studies, used FBS for cultivation (Barberini et al, 2014;Maia et al, 2015;Chang et al, 2016;Tang et al, 2016) and cryopreservation (Mambell et al, 2009;Martinello et al, 2010;Hennes et al, 2015;Figure 3 Median and interquartile range (IQR) of cell viability (a), necrosis (b), early apoptosis (c), and late apoptosis þ necrosis (d) of equine umbilical cord intervascular matrix mesenchymal stem cells (UCIM-MSCs) by flow cytometry before (fresh) and after cryopreservation with medium M1-M4. Asterisks ( Ã ) denote significant differences (P < 0.05) between the fresh cells and treatments (cryopreservation medium: M1-M4).…”

“…Kim et al, 2015;Mun evar et al, 2015;Duan and Lopez, 2016;Ercolin et al, 2016;Irioda et al, 2016) possibly by its positive aspect in cell growth and benefits during freezing. However, it is important to point that for therapeutic purposes, the FBS must be washed out before cell transfer (Maia et al, 2015).…”

Intramuscular Transplantation of Allogeneic Mesenchymal Stromal Cells Derived from Equine Umbilical Cord

“…The stem cell therapies must be safe, which means that besides not causing rejection in the host, should not cause tumors and should be readily harvested and expanded (8). Several researches have been testing the immunogenicity of MSCs in horses and showing their safety in autologous and allogeneic transplants such as intradermal (5), intra-articular (9), intrathecal (10) and intralesional in tendon using BM and amniotic membrane cells (11). Additionally, equine is a good experimental model for extrapolating results to human medicine once it has several similarities to humans when referring to musculoskeletal diseases (12).…”