María Valentina Suárez-Nieto

All Publications

• CNS-wide repopulation by hematopoietic-derived microglia-like cells corrects progranulin deficiency in mice. Nature communications Colella, P., Sayana, R., Suarez-Nieto, M. V., Sarno, J., Nyame, K., Xiong, J., Pimentel Vera, L. N., Arozqueta Basurto, J., Corbo, M., Limaye, A., Davis, K. L., Abu-Remaileh, M., Gomez-Ospina, N. 2024; 15 (1): 5654

  Abstract

  Hematopoietic stem cell transplantation can deliver therapeutic proteins to the central nervous system (CNS) through transplant-derived microglia-like cells. However, current conditioning approaches result in low and slow engraftment of transplanted cells in the CNS. Here we optimized a brain conditioning regimen that leads to rapid, robust, and persistent microglia replacement without adverse effects on neurobehavior or hematopoiesis. This regimen combines busulfan myeloablation and six days of Colony-stimulating factor 1 receptor inhibitor PLX3397. Single-cell analyses revealed unappreciated heterogeneity of microglia-like cells with most cells expressing genes characteristic of homeostatic microglia, brain-border-associated macrophages, and unique markers. Cytokine analysis in the CNS showed transient inductions of myeloproliferative and chemoattractant cytokines that help repopulate the microglia niche. Bone marrow transplant of progranulin-deficient mice conditioned with busulfan and PLX3397 restored progranulin in the brain and eyes and normalized brain lipofuscin storage, proteostasis, and lipid metabolism. This study advances our understanding of CNS repopulation by hematopoietic-derived cells and demonstrates its therapeutic potential for treating progranulin-dependent neurodegeneration.

  View details for DOI 10.1038/s41467-024-49908-4

  View details for PubMedID 38969669

  View details for PubMedCentralID PMC11226701

• Perioperative Regional Anesthesia Pain Outcomes in Children: A Retrospective Study of 3,160 Regional Anesthetics in Routine Practice. The Clinical journal of pain Xie, J., De Souza, E., Perez, F., Suárez-Nieto, M. V., Wang, E., Anderson, T. A. 2023

  Abstract

  Randomized controlled trials indicate regional anesthesia (RA) improves postoperative outcomes with reduced pain and opioid consumption. Therefore, we hypothesized children who received RA, regardless of technique, would have reduced pain/opioid use in routine practice.Using a retrospective cohort, we assessed the association of RA with perioperative outcomes in everyday practice at our academic pediatric hospital. Patients ≤18 years undergoing orthopedic, urologic, or general surgeries with and without RA from 5/2014 to 9/2021 were categorized as single-shot, catheter-based, or no-block. Outcomes included: intraoperative opioid exposure and dose, pre-incision anesthesia time, post anesthesia care unit (PACU) opioid exposure and dose, PACU antiemetic/antipruritic administration, PACU/inpatient pain scores, PACU/inpatient lengths of stay, and cumulative opioid exposure. Regression models estimated the adjusted association of RA with outcomes, controlling for multiple variables.11,292 procedures with 3,160 RAs were included. Compared to no-block group, single-shot and catheter-based blocks were associated with opioid-free intraoperative anesthesia and opioid-free PACU stays. Post-PACU (i.e. while inpatient), single-shot blocks were not associated with improved pain scores or reduced opioid use. Catheter-based blocks were associated with reduced PACU and inpatient opioid use until 24 hours post-op, no difference of opioid use from 24 to 36 hours, and higher probability of use from 36 to 72 hours. RA was not associated with reduced cumulative opioid consumption.Despite adjustment for confounders, the association of RA with pediatric pain/opioid use outcomes was mixed. Further investigation is necessary to maximize the benefits of RA.

  View details for DOI 10.1097/AJP.0000000000001172

  View details for PubMedID 37942728

• CNS Repopulation by Hematopoietic-Derived Microglia-Like Cells Corrects Progranulin deficiency. Research square Colella, P., Sayana, R., Suarez-Nieto, M. V., Sarno, J., Nyame, K., Xiong, J., Vera, L. N., Basurto, J. A., Corbo, M., Limaye, A., Davis, K. L., Abu-Remaileh, M., Gomez-Ospina, N. 2023

  Abstract

  Hematopoietic stem cell transplantation can deliver therapeutic proteins to the CNS through donor-derived hematopoietic cells that become microglia-like cells. However, using standard conditioning approaches, hematopoietic stem cell transplantation is currently limited by low and slow engraftment of microglia-like cells. We report an efficient conditioning regimen based on Busulfan and a six-day course of microglia depletion using the colony-stimulating factor receptor 1 inhibitor PLX3397. Combining Busulfan-myeloablation and transient microglia depletion results in robust, rapid, and persistent microglia replacement by bone marrow-derived microglia-like cells throughout the CNS. Adding PLX3397 does not affect neurobehavior or has adverse effects on hematopoietic reconstitution. Through single-cell RNA sequencing and high-dimensional CyTOF mass cytometry, we show that microglia-like cells are a heterogeneous population and describe six distinct subpopulations. Though most bone-marrow-derived microglia-like cells can be classified as homeostatic microglia, their gene signature is a hybrid of homeostatic/embryonic microglia and border associated-macrophages. Busulfan-myeloablation and transient microglia depletion induce specific cytokines in the brain, ultimately combining myeloid proliferative and chemo-attractive signals that act locally to repopulate microglia from outside the niche. Importantly, this conditioning approach demonstrates therapeutic efficacy in a mouse model of GRN deficiency. Transplanting wild-type bone marrow into Grn-/- mice conditioned with Busulfan plus PLX3397 results in high engraftment of microglia-like cells in the brain and retina, restoring GRN levels and normalizing lipid metabolism.

  View details for DOI 10.21203/rs.3.rs-3263412/v1

  View details for PubMedID 37790525

  View details for PubMedCentralID PMC10543302

• Microglia Replacement with Bone Marrow-Derived Cells after Transient Inhibition of the Colony-Stimulating Factor 1 Receptor (CSF1R) is Superior to Standard Myeloablative Conditioning in Neuropathic Lysosomal Storage Diseases Colella, P., Suarez-Nieto, M., Sayana, R., Poletto, E., Vera, L., Basurto, J., Gomez-Ospina, N. CELL PRESS. 2023: 160-161

  View details for Web of Science ID 001045144200296

• Association of Race and Ethnicity with Pediatric Postoperative Pain Outcomes. Journal of racial and ethnic health disparities Rosenbloom, J. M., De Souza, E., Perez, F. D., Xie, J., Suarez-Nieto, M. V., Wang, E., Anderson, T. A. 2022

  Abstract

  INTRODUCTION: Inequitable variability in healthcare practice negatively affects patient outcomes. Children of color may receive different analgesic medications in the perioperative period, resulting in different outcomes.METHODS: Medical records of children 0 to≤18years old from May 2014 to August 2019 were reviewed. The exposure was racial or ethnic groups: Asian, Black, Hispanic, Pacific Islander, and White non-Hispanic (reference).PRIMARY OUTCOME: post-anesthesia care unit mean pain score.SECONDARY OUTCOMES: inpatient mean pain score; opioid, antiemetic, and antipruritic administration in the post-anesthesia care unit and inpatient ward. The association of race or ethnicity with outcomes was modeled using multilevel logistic regression, adjusting for confounders and covariates.RESULTS: Twenty-nine thousand six hundred fourteen cases are included. In the post-anesthesia care unit, Black, Hispanic, and Pacific Islander children had no significant difference in the odds of receiving opioids or having moderate-severe pain as compared to White non-Hispanic patients; Asian children had lower odds of receiving opioids and lower odds of having a moderate-severe mean pain score. In the inpatient setting, Black, Hispanic, and Pacific Islander children had no significant difference in the odds of receiving opioids or having moderate severe-pain as compared to White non-Hispanic children, but Asian children had lower odds of receiving opioids and of having a moderate-severe mean pain score.CONCLUSIONS: Asian children had lower odds of receiving opioids and having moderate-severe pain postoperatively compared to the White non-Hispanic children. These differences may be a function of variation in patient/caregivers culture or healthcare provider care and warrant further investigation.

  View details for DOI 10.1007/s40615-022-01327-1

  View details for PubMedID 35622316

• Association between regional anesthesia and analgesic outcomes: a single-center retrospective study of 2,761 pediatric regional anesthetics Xie, J. J., De Souza, B., Perez, F. D., Suarez-Nieto, M. V., Wang, E., Anderson, T. A. LIPPINCOTT WILLIAMS & WILKINS. 2021: 934-936

  View details for Web of Science ID 000752526600403