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THE BAND AIDE OF THE BROKEN HEART: THE IMMUNOMODULATORY PROPERTIES OF CORTICAL BONE DERIVED STEM CELLS POST ISCHEMIC INJURY
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2021
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Cell Biology
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http://dx.doi.org/10.34944/dspace/7220
Abstract
The inflammatory response mounted following Myocardial Infarction (MI) is closely coupled to myocardial wound healing. Recent reports have identified a consortium of T-regulatory cells (Tregs) that contain tissue specific regulatory signatures that modulate the homeostasis of the peripheral tissues they populate during times of challenge, with one of these populations occupying the heart following ischemic injury. Unfortunately, the identification of therapeutic modulators that can harness the expansion or preservation of tissue specific Tregs have yet to be identified. Cortical Bone Derived Stem Cells (CBSCs) can engraft in the MI heart long enough to modulate the inflammatory microenvironment of the infarcted heart, making CBSCs an ideal therapeutic to modulate Treg localization and function. Intramyocardial injection of CBSCs into the MI heart expanded pro-reparative TNFRII+ Treg residence in the MI heart during acute (1 week) and chronic (8 weeks) stages of ischemic injury. This pro-reparative Treg cell signature was also observed systemically in the splenic tissue. The ablation of Tregs in a FoxP3DTR transgenic animals model via diphtheria toxin administration or the administration of FTY720 to block Treg localization to the MI heart solicited infarct size expansion and compromised cardiac function. Paracrine profiling of CBSC secretome identified that CBSCs are enrichened in Osteoprotegrin (OPG), a TNFR decoy receptor. The depletion of OPG from CBSC secretome can compromised TNFRII Treg induction (in vitro) and localization in the ischemic heart following MI. CBSCs directly modulate post-MI cardiac inflammation via the direct modulation of Treg phenotype during acute and chronic stages of ischemic injury.
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