Biology subjects

Salgado, A. J.

Publications and source records attributed to Salgado, A. J..

2 recordsLinked to original sources

bioRxiv2025

iPSC derived MSC secretome activates distinct neuroprotective pathways in a preclinical model of Parkinsons disease

Parkinsons disease (PD) is characterized by a progressive loss of dopaminergic neurons, which current therapies fail to address. Mesenchymal stem cells (MSCs) secretome holds promising therapeutic potential; however, the gold standard source - bone marrow (BM) - face scalability limitations. Induced pluripotent stem cells (iPSCs)-derived MSCs (iMSCs) are a rejuvenated and clinically attractive source, yet the effects of their secretome have not been studied in PD. Here, we directly compare the effects of BM-MSCs and iMSCs secretome in a 6-OHDA rat model. Despite few differences in secretome composition, both improved motor function and partially ameliorated anhedonia, but only iMSCs secretome significantly preserved dopaminergic neurons. Proteomic analysis revealed that BM-MSCs secretome activates antioxidant and proteostasis pathways, whereas iMSCs secretome activate broader pro-survival and regenerative pathways, including NRF2-mediated oxidative stress response and mTOR. In addition, iMSC-secretome treatment modulated glutamatergic and GABAergic neurotransmission, suggesting restoration of synaptic homeostasis beyond dopaminergic preservation. These findings demonstrate that iMSCs secretome exerts robust neuroprotective effects and shed light on the mechanisms underlying this scalable and clinically translatable therapy for PD.

neuroscience↗

bioRxiv2024

Lack of Synergistic Outcomes with Roflumilast Combined with Levetiracetam or Adipose Stem Cell Secretome After Spinal Cord Injury

The Spinal Cord Injury (SCI) pathophysiology is highly complex, contributing to a poor prognosis and lack of effective treatments. Previously, we demonstrated that Roflumilast (Rof), leads to functional recovery when tested in a SCI contusion model. However, it is unlikely that Rof treatment on its own could fully restore the spinal cord. Therefore, our objective was to scrutinize the synergistic effects of combining Rof with neuroprotective approaches. Herein we tested two therapies, firstly, Rof combined with Levetiracetam (Lev), and in a second phase, the complementary interplay between Rof and Adipose Stem Cells secretome (Sec). We induced SCI using a weight drop trauma model at the T8 level. Functional recovery was assessed according to the Basso, Beattie, and Bresnahan scale, Activity Box Test, Motor Swimming Test, and Von Frei test. Results indicate that the unilateral use of Rof, Lev, or Sec was effective in promoting functional recovery. However, the combination of Rof + Lev or Rof + Sec did not lead to an improvement in functional outcomes when compared to standalone treatments. Moreover, the combination of Rof + Sec actually led to worst functional outcome than the single treatments. Further studies are needed to find a combinatorial treatment that can lead to superior therapeutic effects with potential clinical application.

neuroscience↗