We successfully generated in vitro human regenerative macrophage self-trasplantation (REMaST®) derived from blood monocytes. Transcriptomic analysis of REMaST® confirm the upregulation, compared to M2 macrophages of neurogenic genes, and related to functions required to wound healing including, ECM-remodelling, angiogenesis, response to hypoxia, immune modulation, detoxification and defence, response to stress, and glucose metabolism. Therefore, we decided to exploit REMaST® neuro-regenerative potential and validate these properties. To evaluate REMaST® neurotrophic and neuroprotective activity, we tested REMaST® capability to promote neural sprouting of mouse dorsal root ganglia (mDRG) and human motor neurons (hMN) derived from human induced Pluripotent Stem Cells (iPSCs). Quantification of MAP2 protein showed that REMaST® co-culture resulted in increased neuronal growth (p<0.5). Moreover, we co-cultured neuronal cells with REMaST® in condition of oxygen and glucose deprivation (OGD) and we quantified LDH release through a biochemical colorimetric assay, as a measure of cellular damage. REMaST® were able to statistically significant decrease neuron death (p<0.5). Successively, to test in vitro REMaST® immunomodulatory property, we decided to investigate iNOS expression, typically upregulated during inflammatory reactions, in M1-polarized macrophages both in monoculture and co-cultured with REMaST®. By Flow Cytometry analysis, we found that REMaST® significantly downregulates iNOS expression in M1 macrophages when co-cultured. These data highlight the REMaST® neural regenerative potential. REMaST® may represent a powerful disease-modifying therapy for CNS lesions the potential regenerative effect of on neural tissue.

In vitro assessment of the Neural Regenerative properties of Regenerative Macrophages (REMaST®) / G. Pruonto, L. Sagripanti, I. Barone, A. Amenta, S. Dolci, E. Rossi, L. Mannino, F. Ciarpella, N. Piazza, B. Savino, P. Bossolasco, G. Fumagalli, M. Locati, I. Decimo, F. Bifari. ((Intervento presentato al convegno FENS Forum 2024 tenutosi a Vienna nel 2024.

In vitro assessment of the Neural Regenerative properties of Regenerative Macrophages (REMaST®)

G. Pruonto;L. Sagripanti;I. Barone;A. Amenta;B. Savino;P. Bossolasco;M. Locati;F. Bifari
2024

Abstract

We successfully generated in vitro human regenerative macrophage self-trasplantation (REMaST®) derived from blood monocytes. Transcriptomic analysis of REMaST® confirm the upregulation, compared to M2 macrophages of neurogenic genes, and related to functions required to wound healing including, ECM-remodelling, angiogenesis, response to hypoxia, immune modulation, detoxification and defence, response to stress, and glucose metabolism. Therefore, we decided to exploit REMaST® neuro-regenerative potential and validate these properties. To evaluate REMaST® neurotrophic and neuroprotective activity, we tested REMaST® capability to promote neural sprouting of mouse dorsal root ganglia (mDRG) and human motor neurons (hMN) derived from human induced Pluripotent Stem Cells (iPSCs). Quantification of MAP2 protein showed that REMaST® co-culture resulted in increased neuronal growth (p<0.5). Moreover, we co-cultured neuronal cells with REMaST® in condition of oxygen and glucose deprivation (OGD) and we quantified LDH release through a biochemical colorimetric assay, as a measure of cellular damage. REMaST® were able to statistically significant decrease neuron death (p<0.5). Successively, to test in vitro REMaST® immunomodulatory property, we decided to investigate iNOS expression, typically upregulated during inflammatory reactions, in M1-polarized macrophages both in monoculture and co-cultured with REMaST®. By Flow Cytometry analysis, we found that REMaST® significantly downregulates iNOS expression in M1 macrophages when co-cultured. These data highlight the REMaST® neural regenerative potential. REMaST® may represent a powerful disease-modifying therapy for CNS lesions the potential regenerative effect of on neural tissue.
giu-2024
Settore BIOS-11/A - Farmacologia
https://forum2024.fensforum.org/
In vitro assessment of the Neural Regenerative properties of Regenerative Macrophages (REMaST®) / G. Pruonto, L. Sagripanti, I. Barone, A. Amenta, S. Dolci, E. Rossi, L. Mannino, F. Ciarpella, N. Piazza, B. Savino, P. Bossolasco, G. Fumagalli, M. Locati, I. Decimo, F. Bifari. ((Intervento presentato al convegno FENS Forum 2024 tenutosi a Vienna nel 2024.
Conference Object
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1150783
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
  • OpenAlex ND
social impact