Background & Aim: After complete spinal cord injury (SCI), the neural tissue fails to repair, causing permanent neurological deficits. Nowadays, no treatments are available to heal the neural parenchy- ma and promote axonal regrowth. In this work, we considered tumor as a successful example in nature of tissue growth. Tumor-microen- vironment promotes tumor growth by generating a specific set of macrophages with pro-tumoral functions. We, therefore generated in vitro tumor-educated macrophages (TEM) endowed with trophic, an- giogenic, ECM-remodelling and immunomodulatory properties. We tested TEM regenerative potential in a mouse model of severe SCI. Methods, Results & Conclusion: We found that adoptive transfer of TEM in severe SCI mice promoted motor recovery, axonal regrowth, angiogenesis, cyst-remodeling, and reduced chronic inflammation. Mechanistically, we identified and functionally validated Rictor as one relevant mediator of TEM therapeutic effects. Collectively, these data showed that TEM are a multitarget disease modifier for severe SCI, and a novel autologous cell therapy exploitable for neural tissue regeneration.
Tissue Engineering: ADOPTIVE TRANSFER OF TUMOR-EDUCATED MACROPHAGES PROMOTE NEURAL TISSUE REGENERATION AND MOTOR RECOVERY FOLLOWING SEVERE SPINAL CORD INJURY
Dolci, S.;Mannino, L.;Campanelli, A.;Bottani, E.;Di Chio, M.;Ciarpella, F.;Busetto, G.;Amenta, A.;Scupoli, M.;Boschi, F.;Malpeli, G.;Decimo, I.
2023-01-01
Abstract
Background & Aim: After complete spinal cord injury (SCI), the neural tissue fails to repair, causing permanent neurological deficits. Nowadays, no treatments are available to heal the neural parenchy- ma and promote axonal regrowth. In this work, we considered tumor as a successful example in nature of tissue growth. Tumor-microen- vironment promotes tumor growth by generating a specific set of macrophages with pro-tumoral functions. We, therefore generated in vitro tumor-educated macrophages (TEM) endowed with trophic, an- giogenic, ECM-remodelling and immunomodulatory properties. We tested TEM regenerative potential in a mouse model of severe SCI. Methods, Results & Conclusion: We found that adoptive transfer of TEM in severe SCI mice promoted motor recovery, axonal regrowth, angiogenesis, cyst-remodeling, and reduced chronic inflammation. Mechanistically, we identified and functionally validated Rictor as one relevant mediator of TEM therapeutic effects. Collectively, these data showed that TEM are a multitarget disease modifier for severe SCI, and a novel autologous cell therapy exploitable for neural tissue regeneration.
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