Jesus Acevedo Cintron

Program: Developmental Regenerative and Stem Cell Biology

Current advisor: Susan Mackinnon, MD

Undergraduate university: University of Puerto Rico-Rio Piedras, 2015

Enrollment year: 2017

Research summary
The role of the inflammatory microenvironment in Acellular Nerve Allografts (ANAs)

Reconstruction of nerve gap injuries continue to pose a challenge. While nerve autografts are still the gold standard to repair nerve gaps, alternatives, including acellular nerve allografts (ANAs), are highly desired. However, the regenerative potential of these alternatives is restricted by their length, with long ANAs (≥4 cm) supporting limited axonal regeneration. Using a sciatic nerve injury model, we are interested in studying and characterizing differences in the formation and morphology of blood vessels formed inside the ANA, the accumulation of immune cells and the expression of cytokines between short (2 cm) and long (4 cm) ANAs. Preliminary data using morphometric histology shows robust nerve regeneration in 2 cm but not 4 cm ANAs, changes in blood vessel morphology and an increase in the infiltration of immune cells in the 4 cm ANAs when compared to the 2 cm ANAs. This suggests an on-going inflammatory process is happening in the 4 cm ANAs and that this process is causing changes in the morphology of the blood vessels and potentially blocking nerve regeneration in long ANAs. Future experiments will focus on identifying the inflammatory and immune cells present inside the long ANAs, and on using drugs to decrease inflammation inside these long ANAs.

Graduate publications
Acevedo Cintrón JA, Hunter DA, Schellhardt L, Pan D, Mackinnon SE, Wood MD. 2024 Limited Nerve Regeneration across Acellular Nerve Allografts (ANAs) Coincides with Changes in Blood Vessel Morphology and the Development of a Pro-Inflammatory Microenvironment. Int J Mol Sci, 25(12):6413. PMCID: PMC11204013

Liebendorfer A, Finnan MJ, Schofield JB, Pinni SL, Acevedo-Cintrón JA, Schellhardt L, Snyder-Warwick AK, Mackinnon SE, Wood MD. 2023 Loss of Gata1 decreased eosinophils, macrophages, and type 2 cytokines in regenerating nerve and delayed axon regeneration after a segmental nerve injury. Exp Neurol, 362():114327. PMCID:

Pan D, Schellhardt L, Acevedo-Cintron JA, Hunter D, Snyder-Warwick AK, Mackinnon SE, Wood MD. 2022 IL-4 expressing cells are recruited to nerve after injury and promote regeneration. Exp Neurol, 347():113909. PMCID: PMC8887027

Sayanagi J, Acevedo-Cintrón JA, Pan D, Schellhardt L, Hunter DA, Snyder-Warwick AK, Mackinnon SE, Wood MD. 2021 Brief Electrical Stimulation Accelerates Axon Regeneration and Promotes Recovery Following Nerve Transection and Repair in Mice. J Bone Joint Surg Am, 103(20):e80. PMCID:

Pan D, Sayanagi J, Acevedo-Cintrón JA, Schellhardt L, Snyder-Warwick AK, Mackinnon SE, Wood MD. 2021 Liposomes embedded within fibrin gels facilitate localized macrophage manipulations within nerve. J Neurosci Methods, 348():108981. PMCID: PMC8243038

Pan D, Acevedo-Cintrón JA, Sayanagi J, Snyder-Warwick AK, Mackinnon SE, Wood MD. 2020 The CCL2/CCR2 axis is critical to recruiting macrophages into acellular nerve allograft bridging a nerve gap to promote angiogenesis and regeneration. Exp Neurol, 331():113363. PMCID: PMC7484126