Sickle cell disease patient plasma sensitizes iPSC-derived sensory neurons from sickle cell disease patients. bioRxiv 2023 Jan 10
Date
01/31/2023Pubmed ID
36711992Pubmed Central ID
PMC9882050DOI
10.1101/2023.01.10.523446Abstract
Individuals living with sickle cell disease (SCD) experience severe recurrent acute and chronic pain. In order to develop novel therapies, it is necessary to better understand the neurobiological mechanisms underlying SCD pain. There are many barriers to gaining mechanistic insight into pathogenic SCD pain processes, such as differential gene expression and function of sensory neurons between humans and mice with SCD, as well as the limited availability of patient samples. These can be overcome by utilizing SCD patient-derived induced pluripotent stem cells (iPSCs) differentiated into sensory neurons (SCD iSNs). Here, we characterize the key gene expression and function of SCD iSNs to establish a model for higher-throughput investigation of intrinsic and extrinsic factors that may contribute to increased SCD patient pain. Importantly, identified roles for C-C Motif Chemokine Ligand 2 (CCL2) and endothelin 1 (ET1) in SCD pain can be recapitulated in SCD iSNs. Further, we find that plasma taken from SCD patients during acute pain increases SCD iSN calcium response to the nociceptive stimulus capsaicin compared to those treated with paired SCD patient plasma at baseline or healthy control plasma samples. Together, these data provide the framework necessary to utilize iSNs as a powerful tool to investigate the neurobiology of SCD and identify potential intrinsic mechanisms of SCD pain which may extend beyond a blood-based pathology.
Author List
Allison RL, Burand A, Torres DN, Brandow AM, Stucky CL, Ebert ADAuthors
Amanda Brandow DO Professor in the Pediatrics department at Medical College of WisconsinAllison D. Ebert PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Cheryl L. Stucky PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
