Internalization of nanopolymeric tracers does not alter characteristics of placental cells

Abstract

In the cell therapy scenario, efficient tracing of transplanted cells is essential for investigating cell migration and interactions with host tissues. This is fundamental to provide mechanistic insights which altogether allow for the understanding of the translational potential of placental cell therapy in the clinical setting. Mesenchymal stem/stromal cells (MSC) from human placenta are increasingly being investigated for their potential in treating patients with a variety of diseases. In this study, we investigated the feasibility of using poly (methyl methacrylate) nanoparticles (PMMA‐NPs) to trace placental MSC, namely those from the amniotic membrane (hAMSC) and early chorionic villi (hCV‐MSC). We report that PMMP‐NPs are efficiently internalized and retained in both populations, and do not alter cell morphofunctional parameters. We observed that PMMP‐NP incorporation does not alter in vitro immune modulatory capability of placental MSC, a characteristic central to their reparative/therapeutic effects in vitro. We also show that in vitro, PMMP‐NP uptake is not affected by hypoxia. Interestingly, after in vivo brain ischaemia and reperfusion injury achieved by transient middle cerebral artery occlusion (tMCAo) in mice, iv hAMSC treatment resulted in significant improvement in cognitive function compared to PBS‐treated tMCAo mice. Our study provides evidence that tracing placental MSC with PMMP‐NPs does not alter their in vitro and in vivo functions. These observations are grounds for the use of PMMP‐NPs as tools to investigate the therapeutic mechanisms of hAMSC and hCV‐MSC in preclinical models of inflammatory‐driven diseases.

Intravenous infusion of human bone marrow mesenchymal stromal cells promotes functional recovery and neuroplasticity after ischemic stroke in mice

“…In our study we obtained beneficial effects after systemic infusion of hBM-MSC. We did not investigate the presence of the infused cells in the brain, however we tracked IV infused hMSC in a previous study and showed that hMSC loaded with nanoparticles were detectable in the lungs up to 48 h after surgery, while no cells were found in the brain at 48 h or later time points 71 . Nevertheless infused hMSC produce long-lasting changes as shown by the improvement in anxious behavior, recognition memory performance and sensorimotor function 5w after injury compared to tMCAo PBS mice.…”

“…Anesthesia was induced by 3% isoflurane inhalation in an N 2 O/O 2 (70/30%) mixture and maintained by 1 to 1.5% isoflurane inhalation in an N 2 O/O 2 (70/30%) mixture. Transient ischemia was achieved by tMCAo by means of a siliconized filament (7-0, Doccol Corporation) introduced into the internal carotid artery and advanced to block the MCA for 60 minutes 71 . Sham-operated mice received identical anesthesia and surgery without artery occlusion.…”

“…Recognition memory was assessed during the test phase and expressed as a discrimination index (DI), i.e., (seconds spent on novel −seconds spent on familiar)/(total time spent on objects). Animals with no memory impairment spent a longer time investigating the novel object, giving a higher DI 71 , 92 .…”

Placenta-Derived Cells for Acute Brain Injury

“…As regards amniotic cells, the epithelial population amniotic epithelial cells (AECs), isolated from rat 32 or human 64 tissues, can migrate to the site of ischemic injury 32 and improve functional recovery after MCAO 64 . hAMSCs can also improve functional recovery after MCAO 65 , 66 , accelerated by overexpression of BDNF 67 .…”