Modeling cellular responses to serum and vitamin D in microgravity using a human kidney microphysiological system

Area of Science:

• Space biology
• Renal physiology
• Cellular toxicology

Background:

• Microgravity on the International Space Station (ISS) offers insights into cellular pathology relevant to disease on Earth.
• Kidney proximal tubule epithelial cells (PTECs) are crucial for vitamin D activation and waste filtration.

Purpose of the Study:

• To investigate microgravity's effects on PTEC response to serum exposure and vitamin D metabolism.
• To assess potential kidney toxicity and inflammation markers under microgravity conditions.

Main Methods:

• Kidney proximal tubule epithelial cells (PTECs) were cultured in a microphysiological system (PT-MPS) and exposed to human serum.
• Vitamin D biotransformation and gene expression (CYP27B1, CYP24A1, CYP3A5) were analyzed in 3D PTEC cultures.
• Global transcriptomics (RNAseq) and toxicity/inflammation biomarkers (KIM-1, IL-6) were measured.

Main Results:

• Microgravity did not alter vitamin D metabolite formation in PTECs.
• No unique PTEC response to human serum was observed under microgravity.
• Key kidney proximal tubule biochemical pathways remained unaffected by short-term microgravity exposure.

Conclusions:

• Short-term microgravity exposure does not significantly impact fundamental kidney proximal tubule functions like vitamin D metabolism or response to serum.
• Further research is needed to determine if these findings hold for extended spaceflight durations (>6 months).