We have recently demonstrated that heterologous transplantation of horse amniotic membrane-derived cells (AMCs) can be useful for cell therapy applications in tendon diseases, and hypothesized that these cells may promote tendon repair via paracrine-acting molecules targeting inflammatory processes. To test this hypothesis, here we examined the immunomodulatory characteristics of AMCs and of their conditioned medium (AMCs-CM) in vitro, and studied the potential therapeutic effect of AMCs-CM in thirteen different spontaneous horse tendon and ligament injuries in vivo. Our results demonstrate that AMCs are capable of inhibiting PBMC proliferation after allogenic stimulation either when co-cultured in cell-to-cell contact, or when the two cell types are physically separated by a transwell membrane, suggesting that soluble factors are implicated in this phenomenon. Our hypothesis is further supported by the demonstration that peripheral blood mononuclear cells (PBMC) proliferation is inhibited by AMCs-CM. In our in vivo studies, no significant adverse effects were observed in treated tendons, and clinical and ultrasonographical evaluation did not reveal evidence of inappropriate tissue or tumor formation. Clinical outcomes were favorable and the significantly lower rate (15.38%) of re-injuries observed compared to untreated animals, suggests that treatment with AMCs-CM is very efficacious. In conclusion, this study identifies AMCs-CM as a novel therapeutic biological cell-free product for treating horse tendon and ligament diseases.
Conditioned medium from horse amniotic membrane-derived multipotent progenitor cells: immunomodulatory activity in vitro and first clinical application in tendon and ligament injuries in vivo / A. Lange Consiglio, D. Rossi, S. Tassan, R. Perego, F. Cremonesi, O. Parolini. - In: STEM CELLS AND DEVELOPMENT. - ISSN 1547-3287. - 22:22(2013 Nov 15), pp. 3015-3024. [10.1089/scd.2013.0214]
Conditioned medium from horse amniotic membrane-derived multipotent progenitor cells: immunomodulatory activity in vitro and first clinical application in tendon and ligament injuries in vivo
A. Lange ConsiglioPrimo
;R. Perego;F. Cremonesi
;
2013
Abstract
We have recently demonstrated that heterologous transplantation of horse amniotic membrane-derived cells (AMCs) can be useful for cell therapy applications in tendon diseases, and hypothesized that these cells may promote tendon repair via paracrine-acting molecules targeting inflammatory processes. To test this hypothesis, here we examined the immunomodulatory characteristics of AMCs and of their conditioned medium (AMCs-CM) in vitro, and studied the potential therapeutic effect of AMCs-CM in thirteen different spontaneous horse tendon and ligament injuries in vivo. Our results demonstrate that AMCs are capable of inhibiting PBMC proliferation after allogenic stimulation either when co-cultured in cell-to-cell contact, or when the two cell types are physically separated by a transwell membrane, suggesting that soluble factors are implicated in this phenomenon. Our hypothesis is further supported by the demonstration that peripheral blood mononuclear cells (PBMC) proliferation is inhibited by AMCs-CM. In our in vivo studies, no significant adverse effects were observed in treated tendons, and clinical and ultrasonographical evaluation did not reveal evidence of inappropriate tissue or tumor formation. Clinical outcomes were favorable and the significantly lower rate (15.38%) of re-injuries observed compared to untreated animals, suggests that treatment with AMCs-CM is very efficacious. In conclusion, this study identifies AMCs-CM as a novel therapeutic biological cell-free product for treating horse tendon and ligament diseases.File | Dimensione | Formato | |
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