Exosomes derived from mesenchymal stem cells repair a Parkinson’s disease model by inducing autophagy

Abstract

Parkinson's disease (PD) is a progressively debilitating neurodegenerative condition that leads to motor and cognitive dysfunction. At present, clinical treatment can only improve symptoms, but cannot effectively protect dopaminergic neurons. Several reports have demonstrated that human umbilical cord mesenchymal stem cells (hucMSCs) afford neuroprotection, while their application is limited because of their uncontrollable differentiation and other reasons. Stem cells communicate with cells through secreted exosomes (Exos), the present study aimed to explore whether Exos secreted by hucMSCs could function instead of hucMSCs. hucMSCs were successfully isolated and characterized, and shown to contribute to 6-hydroxydopamine (6-OHDA)-stimulated SH-SY5Y cell proliferation; hucMSC-derived Exos were also involved in this process. The Exos were purified and identified, and then labeled with PKH 26, it was found that the Exos could be efficiently taken up by SH-SY5Y cells after 12 h of incubation. Pretreatment with Exos promoted 6-OHDA-stimulated SH-SY5Y cells to proliferate and inhibited apoptosis by inducing autophagy. Furthermore, Exos reached the substantia nigra through the blood-brain barrier (BBB) in vivo, relieved apomorphine-induced asymmetric rotation, reduced substantia nigra dopaminergic neuron loss and apoptosis, and upregulated the level of dopamine in the striatum. These results demonstrate that hucMSCs-Exos have a treatment capability for PD and can traverse the BBB, indicating their potential for the effective treatment of PD.

Retroviral Infection of Human Neurospheres and Use of Stem Cell EVs to Repair Cellular Damage

“…IL6, IL8, IL1β, TNFα, IFNα) that can further exacerbate the inflammatory response [60,114]. In recent years, the neuroprotective and anti-inflammatory properties of stem cell EVs have been well-documented; in the context of the CNS, there is accumulating evidence that stem cell EVs may be able to reverse neuronal apoptosis and modulate the polarization of both astrocytes and microglia from pro-inflammatory to anti-inflammatory phenotypes [81,82,83,84,85,86,87,88,89,90,91,92]. To the best of our knowledge, the functional effects of stem cell EVs on 3D cultures has not previously been reported.…”

“…After confirming EV uptake by neurospheres we shifted our focus to next examine their potential functional effects in HIV-1 infected neurospheres. To date, the anti-apoptotic effects of stem cell EVs in the context of the CNS have been well documented both in vitro and in vivo [81,82,83,84,85,86]. To this end, we performed western blot to examine the expression levels of different proteins involved in the regulation of apoptosis ( Fig.…”

Stem Cell-Derived Exosomes as Therapeutic Approach for Neurodegenerative Disorders: From Biology to Biotechnology

“…A similar approach was also evaluated for delivering dopamine to the striatum and substantia nigra of PD mouse model, confirming that the exosomes can be used as a promising drug delivery platform for target therapy against PD and other neurodegenerative diseases [ 145 ]. In a current study, Chen et al demonstrated that human umbilical cord mesenchymal stem cells (hucMSC)-derived exosomes can reach the substantia nigra through the BBB in vivo, reducing the dopaminergic neuron loss and apoptosis and upregulating the levels of dopamine in the striatum [ 146 ].…”

Insights into the Effects of Mesenchymal Stem Cell-Derived Secretome in Parkinson’s Disease

“…A research group demonstrated that human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes reduced apoptosis in SH-SY5Y cell culture. Further, in a PD rat model (6-OHDA lesioned), exosomes crossing the blood-brain barrier, reached the substantia nigra, decreased dopaminergic neurons loss and apoptosis, improved apomorphine-induced asymmetric rotation, and increased dopamine levels in the striatum [ 81 ].…”