Engineering topics

Racheli Ofir

Publications and source records attributed to Racheli Ofir.

3 records

NASA NTRS2021

The Effects of Simulated Microgravity and PLacental-EXpanded (PLX-PAD) Stromal Cell Treatment on The Behavior and Correlation with Cytokine Profiles in Female Mice

Spacelight can lead to altered immune responses and inflammation (Crucian et al. 2014) and elevated levels of inflammation are connected to anxiety and depression. A recent study on the International Space Station showed that mice exhibited a novel circling behavior during spaceflight (Ronca 2019). However, there is still a gap in knowledge on how microgravity impacts behavior. In this current study, we performed 30 days of hindlimb unloading (HU) on four-month old female mice and analyzed select behavior from video image capture. We also determined the effects of PLacental-eXpanded stromal cells dervided from the maternal placenta (PLX-PAD), alone and in combination with HU and isolation, on behavior. We have previoulst shown that PLX-PAD mitigated select inflammatory responses and changes in cytokine expression causes by HU. In-cage behaviors were analyzed in HU or control female mice treated with 2 injections of PlasmaLyte (Sham) or PLX-PAD (n=7/group). We found that PLX-PAD decreased exploratory behaviors compared to Sham treated mice at night. Normally loaded (NL) PLX mice slept less than NL Sham mice during the day, and HU animals had signficantly higher involuntary movement during sleep compared to NL animals, suggesting sleep distruption. Overall, we show that both HU and PLX affect important behavioral factors., This experiment is the first to study the effects of PLX-PAD on behavior. Additional studies are needed to define the behavioral changes in spaceflight and test possible countermeasures. Funding for this project was provided through the 2019 Ames Research Innovation Award (ARIA) provided by NASA Ames Research Center.

Stromal cell treatment↗

NASA NTRSDate not supplied

The Effects of Placental-expanded (PLX-PAD) Stromal Cell Treatment, Hindlimb Unloading, and Isolation on the Behavior of Female Mice

Spaceflight can lead to altered immune responses and inflammation (Crucian et al. 2014) and elevated levels of inflammation are connected to anxiety and depression. A recent study on the International Space Station showed that mice exhibited a novel circling behavior during spaceflight (Ronca et al. 2019). However, there is still a gap in knowledge on how microgravity impacts behavior. In this current study, we performed 30 days of hindlimb unloading (HU) on four-month old female mice and analyzed select behavior from video image capture. We also determined the effects of PLacental-eXpanded stromal cells derived from the maternal placenta (PLX-PAD), alone and in combination with HU and isolation, on behavior. We have previously shown that PLX-PAD mitigates select inflammatory responses and changes in cytokine expression caused by HU. In-cage behaviors were analyzed in HU or control female mice treated with 2 injections of PlasmaLyte (Sham) or PLX-PAD (n=7/group). We found that PLX-PAD decreased exploratory behaviors compared to Sham-treated mice at night. Normally loaded (NL) PLX mice slept less than NL Sham mice during the day, and HU animals had significantly higher involuntary movement during sleep compared to NL animals, suggesting sleep disruption. Overall, we show that both HU and PLX affect important behavioral factors. This experiment is the first to study the effects of PLX-PAD on behavior. Additional studies are needed to define the behavioral changes in spaceflight and test possible countermeasures.

PLacental-EXpanded stromal cells, behavior, microg↗

NASA NTRSDate not supplied

Human placenta-derived stromal cells mitigate select immune responses to simulated weightlessness

Space flight presents unique risks to human health. Microgravity and social isolation are important space flight stressors which have vast impact on multiple systems such as the musculoskeletal, immune and central nervous system (CNS). To explore candidate countermeasures against tissue decrements caused by spaceflight, we performed a pilot study with PLacental-eXpanded stromal (PLX) cells. PLX cells secrete factors that modulate the immune system, but do not trigger host immune responses, enabling treatment in subjects that have intact immune systems. These cells had previous success in treating critical limb ischemia and acute radiation syndrome in murine models. In this study, 4-month-old female mice underwent 30 days of hindlimb unloading (HU) in single housing conditions to simulate long-term weightlessness and isolation. HU and normally ambulating controls were administered with PLX cells or sham-injected with Plasmalyte. We hypothesized that administration of PLX cells will mitigate some of the effects caused by prolonged HU. We found that treatment with PLX cells was well tolerated as indicated by body weights, circulating corticosterone levels and immune organ response to injection of the cells. HU led to the expected decreases in soleus muscle weights and bone loss. We did not observe any protective properties of the PLX cells in the musculoskeletal system but found that the cell treatment partially protected from a subset of HU-induced immune and CNS changes. In the hippocampus, protein levels of 9 of 44 cytokines were downregulated by HU. PLX administration mitigated changes in expression of 8 of these cytokines, including IL-2, IL-6 and MCP-1. To our knowledge, this is the first report on the protective effects of PLX-PAD against HU-induced changes in the cytokine milieu of the CNS. Our findings warrant further studies, which includes testing in actual spaceflight.

Microgravity↗