Mesenchymal Progenitors in the Epidural Fat and Dura Mater Participate in Tissue Homeostasis and Wound Healing
Date
2021-07-12
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Abstract
Mesenchymal progenitor cells (MPCs) are adult cells capable of self-renewal and differentiation into cells that make up mesodermal tissues such as bone, cartilage, and fat. MPCs are believed to play a significant role in tissue maintenance and repair. MPCs are present in many adult connective tissues but are typically found in higher quantities in adipose tissues for yet unknown reasons. Recently, our research group identified MPC populations within epidural fat and the adjacent dura mater. Clinically, epidural fat is frequently considered a space-filling, biologically inert tissue; therefore, it is common practice for spine surgeons to discard it during surgical procedures. As the development and cellular origins of both epidural fat and the dura mater remain unclear, I hypothesized that epidural fat MPCs contribute to the maintenance of dural integrity throughout growth and post-injury. Using Paired related homeobox 1 (Prx1) and Hypermethylated in cancer 1 (Hic1) transgenic lineage tracing mice, the localization of epidural fat MPCs were identified during normal maturation and at skeletal maturity. This lineage tracing revealed an overlap between Prx1+ and Hic1+ populations, indicating a potential hierarchical relationship between the two MPC populations. When Prx1+/ Hic1+ MPCs were ablated, the expression of the dural marker α-SMA was lost in adjacent dura mater suggesting these cells are required for tissue homeostasis. Both MPC populations were observed to respond to dural injuries by homing to the lesion site. The process by which epidural fat MPCs maintain the dura mater through growth and after injury was accelerated in p21-/- mice (known for increased tissue regeneration/ cell proliferation). While MPCs have been identified and characterized in other adipose tissues, the role in epidural fat remained elusive. This study contributed to our knowledge of the role of epidural fat MPCs in vivo in aspects of growth, homeostasis, and repair of dural tissue. This thesis emphasizes the importance of revisiting the prevalent notion of epidural fat as biologically insignificant and the process of discarding it during surgery.
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mesenchymal progenitor cells, dura mater, spine microenvironment, tissue repair/maintenance, regenerative medicine, animal models, Cre-loxP system, epidural fat, in vivo tracing
Citation
Shah, S. (2021). Mesenchymal Progenitors in the Epidural Fat and Dura Mater Participate in Tissue Homeostasis and Wound Healing (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.