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30 results on '"Diaz Deleon, Nestor M."'

1. Piezo inhibition preventsandrescues scarring by targeting the adipocyte to fibroblast transition

Author

Griffin, Michelle F., primary, Talbott, Heather E., additional, Guardino, Nicholas J., additional, Guo, Jason L., additional, Spielman, Amanda F., additional, Chen, Kellen, additional, Parker, Jennifer B.L., additional, Mascharak, Shamik, additional, Henn, Dominic, additional, Liang, Norah, additional, King, Megan, additional, Cotterell, Asha C., additional, Bauer-Rowe, Khristian E., additional, Abbas, Darren B., additional, Diaz Deleon, Nestor M., additional, Sivaraj, Dharshan, additional, Fahy, Evan J., additional, Downer, Mauricio, additional, Akras, Deena, additional, Berry, Charlotte, additional, Cook, Jessica, additional, Quarto, Natalina, additional, Klein, Ophir D., additional, Lorenz, H. Peter, additional, Gurtner, Geoffrey C., additional, Januszyk, Michael, additional, Wan, Derrick C., additional, and Longaker, Michael T., additional

Published
2023
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2. Decellularized Adipose Matrices Can Alleviate Radiation-Induced Skin Fibrosis

Author

Adem, Sandeep, primary, Abbas, Darren B., additional, Lavin, Christopher V., additional, Fahy, Evan J., additional, Griffin, Michelle, additional, Diaz Deleon, Nestor M., additional, Borrelli, Mimi R., additional, Mascharak, Shamik, additional, Shen, Abra H., additional, Patel, Ronak A., additional, Longaker, Michael T., additional, Nazerali, Rahim S., additional, and Wan, Derrick C., additional

Published
2022
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3. Understanding Scarring in the Oral Mucosa

Author

Griffin, Michelle F., primary, Fahy, Evan J., additional, King, Megan, additional, Guardino, Nicholas, additional, Chen, Kellen, additional, Abbas, Darren B., additional, Lavin, Christopher V., additional, Diaz Deleon, Nestor M., additional, Lorenz, H. Peter, additional, Longaker, Michael T., additional, and Wan, Derrick C., additional

Published
2022
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5. Disrupting mechanotransduction decreases fibrosis and contracture in split-thickness skin grafting

Author

Chen, Kellen, primary, Henn, Dominic, additional, Januszyk, Michael, additional, Barrera, Janos A., additional, Noishiki, Chikage, additional, Bonham, Clark A., additional, Griffin, Michelle, additional, Tevlin, Ruth, additional, Carlomagno, Theresa, additional, Shannon, Tara, additional, Fehlmann, Tobias, additional, Trotsyuk, Artem A., additional, Padmanabhan, Jagannath, additional, Sivaraj, Dharshan, additional, Perrault, David P., additional, Zamaleeva, Alsu I., additional, Mays, Chyna J., additional, Greco, Autumn H., additional, Kwon, Sun Hyung, additional, Leeolou, Melissa C., additional, Huskins, Savana L., additional, Steele, Sydney R., additional, Fischer, Katharina S., additional, Kussie, Hudson C., additional, Mittal, Smiti, additional, Mermin-Bunnell, Alana M., additional, Diaz Deleon, Nestor M., additional, Lavin, Christopher, additional, Keller, Andreas, additional, Longaker, Michael T., additional, and Gurtner, Geoffrey C., additional

Published
2022
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12. Dermal Iron Chelation Reduces Indirect Radiation Injury

Author

Lavin, Christopher V., primary, Fahy, Evan J., additional, Abbas, Darren B., additional, griffin, michelle, additional, Lee, Daniel K., additional, Diaz Deleon, Nestor M., additional, Guardino, Nicholas, additional, Gurtner, Geoffrey C., additional, Longaker, Michael T., additional, and Wan, Derrick C., additional

Published
2021
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14. A comparative analysis of deferoxamine treatment modalities for dermal radiation‐induced fibrosis

Author

Lavin, Christopher V., primary, Abbas, Darren B., additional, Fahy, Evan J., additional, Lee, Daniel K., additional, Griffin, Michelle, additional, Diaz Deleon, Nestor M., additional, Mascharak, Shamik, additional, Chen, Kellen, additional, Momeni, Arash, additional, Gurtner, Geoffrey C., additional, Longaker, Michael T., additional, and Wan, Derrick C., additional

Published
2021
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15. JUN promotes hypertrophic skin scarring via CD36 in preclinical in vitro and in vivo models

Author

Griffin, Michelle F., primary, Borrelli, Mimi R., additional, Garcia, Julia T., additional, Januszyk, Michael, additional, King, Megan, additional, Lerbs, Tristan, additional, Cui, Lu, additional, Moore, Alessandra L., additional, Shen, Abra H., additional, Mascharak, Shamik, additional, Diaz Deleon, Nestor M., additional, Adem, Sandeep, additional, Taylor, Walter L., additional, desJardins-Park, Heather E., additional, Gastou, Marc, additional, Patel, Ronak A., additional, Duoto, Bryan A., additional, Sokol, Jan, additional, Wei, Yuning, additional, Foster, Deshka, additional, Chen, Kellen, additional, Wan, Derrick C., additional, Gurtner, Geoffrey C., additional, Lorenz, Hermann P., additional, Chang, Howard Y., additional, Wernig, Gerlinde, additional, and Longaker, Michael T., additional

Published
2021
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18. The antifibrotic adipose-derived stromal cell: Grafted fat enriched with CD74+ adipose-derived stromal cells reduces chronic radiation-induced skin fibrosis

Author

Borrelli, Mimi R., primary, Patel, Ronak A., additional, Adem, Sandeep, additional, Diaz Deleon, Nestor M., additional, Shen, Abra H., additional, Sokol, Jan, additional, Yen, Sara, additional, Chang, Erin Y., additional, Nazerali, Rahim, additional, Nguyen, Dung, additional, Momeni, Arash, additional, Wang, Kevin C., additional, Longaker, Michael T., additional, and Wan, Derrick C., additional

Published
2020
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19. CD34+CD146+ adipose-derived stromal cells enhance engraftment of transplanted fat

Author

Borrelli, Mimi R., primary, Patel, Ronak A., additional, Blackshear, Charles, additional, Vistnes, Stephanie, additional, Diaz Deleon, Nestor M., additional, Adem, Sandeep, additional, Shen, Abra H., additional, Sokol, Jan, additional, Momeni, Arash, additional, Nguyen, Dung, additional, Longaker, Michael T., additional, and Wan, Derrick C., additional

Published
2020
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20. Abstract 106

Author

Shen, Abra H., primary, Borrelli, Mimi R., additional, Mascharak, Shamik, additional, Diaz Deleon, Nestor M., additional, Adem, Sandeep, additional, Wan, Derrick C., additional, Longaker, Michael T., additional, and Peter Lorenz, H., additional

Published
2020
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21. Abstract 155

Author

Diaz Deleon, Nestor M., primary, Borrelli, Mimi R., additional, Adem, Sandeep, additional, Shen, Abra H., additional, Longaker, Michael T., additional, and Wan, Derrick C., additional

Published
2020
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22. Abstract 99

Author

Shen, Abra H., primary, Borrelli, Mimi R., additional, Januszyk, Michael, additional, Diaz Deleon, Nestor M., additional, Adem, Sandeep, additional, Gurtner, Geoffrey C., additional, Wan, Derrick C., additional, and Longaker, Michael T., additional

Published
2020
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23. Abstract 152

Author

Borrelli, Mimi R., primary, Adem, Sandeep, additional, Diaz Deleon, Nestor M., additional, Januszyk, Michael, additional, Nguyen, Dung, additional, Momeni, Arash, additional, Longaker, Michael T., additional, and Wan, Derrick C., additional

Published
2020
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24. Abstract 1

Author

Adem, Sandeep, primary, Borrelli, Mimi R., additional, Chen, Kellen, additional, Diaz Deleon, Nestor M., additional, Shen, Abra H., additional, Noishiki, Chikage, additional, Gurtner, Geoffrey C., additional, Longaker, Michael T., additional, and Wan, Derrick C., additional

Published
2020
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25. Fat grafting rescues radiation-induced joint contracture

Author

Borrelli, Mimi R., primary, Diaz Deleon, Nestor M., additional, Adem, Sandeep, additional, Patel, Ronak A., additional, Mascharak, Shamik, additional, Shen, Abra H., additional, Irizarry, Dre, additional, Nguyen, Dung, additional, Momeni, Arash, additional, Longaker, Michael T., additional, and Wan, Derrick C., additional

Published
2019
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26. The antifibrotic adipose‐derived stromal cell: Grafted fat enriched with CD74+ adipose‐derivedstromal cells reduces chronic radiation‐induced skin fibrosis

Author

Borrelli, Mimi R., Patel, Ronak A., Adem, Sandeep, Diaz Deleon, Nestor M., Shen, Abra H., Sokol, Jan, Yen, Sara, Chang, Erin Y., Nazerali, Rahim, Nguyen, Dung, Momeni, Arash, Wang, Kevin C., Longaker, Michael T., and Wan, Derrick C.

Abstract

Fat grafting can reduce radiation‐induced fibrosis. Improved outcomes are found when fat grafts are enriched with adipose‐derived stromal cells (ASCs), implicating ASCs as key drivers of soft tissue regeneration. We have identified a subpopulation of ASCs positive for CD74 with enhanced antifibrotic effects. Compared to CD74− and unsorted (US) ASCs, CD74+ ASCs have increased expression of hepatocyte growth factor, fibroblast growth factor 2, and transforming growth factor β3 (TGF‐β3) and decreased levels of TGF‐β1. Dermal fibroblasts incubated with conditioned media from CD74+ ASCs produced less collagen upon stimulation, compared to fibroblasts incubated with media from CD74− or US ASCs. Upon transplantation, fat grafts enriched with CD74+ ASCs reduced the stiffness, dermal thickness, and collagen content of overlying skin, and decreased the relative proportions of more fibrotic dermal fibroblasts. Improvements in several extracellular matrix components were also appreciated on immunofluorescent staining. Together these findings indicate CD74+ ASCs have antifibrotic qualities and may play an important role in future strategies to address fibrotic remodeling following radiation‐induced fibrosis. CD74⩲ adipose‐derived stromal cells express multiple growth factors with antifibrotic activity. These cells decrease production of collagen type 1 by TGF‐B1 stimulated fibroblasts, and when used to enrich fat grafts, they promote remodeling of radiation‐induced fibrosis in the overlying skin.CD74⩲ adipose‐derived stromal cells express multiple growth factors with antifibrotic activity. These cells decrease production of collagen type 1 by TGF‐B1 stimulated fibroblasts, and when used to enrich fat grafts, they promote remodeling of radiation‐induced fibrosis in the overlying skin.

Published
2020
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27. Fat grafting rescues radiation‐induced joint contracture

Author

Borrelli, Mimi R., Diaz Deleon, Nestor M., Adem, Sandeep, Patel, Ronak A., Mascharak, Shamik, Shen, Abra H., Irizarry, Dre, Nguyen, Dung, Momeni, Arash, Longaker, Michael T., and Wan, Derrick C.

Abstract

The aim of this study was to explore the therapeutic effects of fat grafting on radiation‐induced hind limb contracture. Radiation therapy (RT) is used to palliate and/or cure a range of malignancies but causes inevitable and progressive fibrosis of surrounding soft tissue. Pathological fibrosis may lead to painful contractures which limit movement and negatively impact quality of life. Fat grafting is able to reduce and/or reverse radiation‐induced soft tissue fibrosis. We explored whether fat grafting could improve extensibility in irradiated and contracted hind limbs of mice. Right hind limbs of female 60‐day‐old CD‐1 nude mice were irradiated. Chronic skin fibrosis and limb contracture developed. After 4 weeks, irradiated hind limbs were then injected with (a) fat enriched with stromal vascular cells (SVCs), (b) fat only, (c) saline, or (d) nothing (n = 10/group). Limb extension was measured at baseline and every 2 weeks for 12 weeks. Hind limb skin then underwent histological analysis and biomechanical strength testing. Irradiation significantly reduced limb extension but was progressively rescued by fat grafting. Fat grafting also reduced skin stiffness and reversed the radiation‐induced histological changes in the skin. The greatest benefits were found in mice injected with fat enriched with SVCs. Hind limb radiation induces contracture in our mouse model which can be improved with fat grafting. Enriching fat with SVCs enhances these beneficial effects. These results underscore an attractive approach to address challenging soft tissue fibrosis in patients following RT. Fat grafting reduces radiation‐induced hind limb contracture.

Published
2020
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28. Decellularized Adipose Matrices can Alleviate Radiation-induced Skin Fibrosis

Author

Adem, Sandeep, Abbas, Darren B, Lavin, Christopher, Fahy, Evan, griffin, michelle, Diaz Deleon, Nestor M, Borrelli, Mimi R, Mascharak, Shamik, Shen, Abra H., Patel, Ronak A., Longaker, Michael T, Nazerali, Rahim S., and Wan, Derrick C

Abstract

Objective: Radiation therapy is commonplace for cancer treatment but often results in fibrosis and atrophy of surrounding soft tissue. Decellularized adipose matrices (DAMs) have been reported to improve these soft tissue defects through the promotion of adipogenesis. These matrices are decellularized by a combination of physical, chemical, and enzymatic methods to minimize their immunologic effects while promoting their regenerative effects. In this study, we aimed to explore the regenerative ability of a DAM (Renuva®, MTF Biologics, New Jersey, USA) in radiation-induced soft tissue injury. Approach: Fresh human lipoaspirate or DAM was injected into the irradiated scalp of CD-1 nude mice, and volume retention was monitored radiographically over 8 weeks. Explanted grafts were histologically assessed, and overlying skin was examined histologically and biomechanically. Irradiated human skin was also evaluated from patients following fat grafting or DAM injection. However, integrating data between murine and human skin in all cohorts is limited given the genetic variability between the two species. Results: Volume retention was found to be greater with fat grafts, though DAM retention was nonetheless appreciated at irradiated sites. Improvement in both mouse and human irradiated skin overlying fat and DAM grafts was observed in terms of biomechanical stiffness, dermal thickness, collagen density, collagen fiber networks, and skin vascularity. Innovation: This is the first demonstration of the use of DAMs for augmenting the regenerative potential of irradiated mouse and human skin. Conclusions: These findings support use of DAMs to address soft tissue atrophy following radiation therapy. Morphological characteristics of the irradiated skin can also be improved with DAM grafting.

Published
2021
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29. A tension offloading patch mitigates dermal fibrosis induced by pro-fibrotic skin injections.

Author

Talbott HE, Griffin MF, Mascharak S, Parker JBL, Kuhnert MM, Guo JL, Diaz Deleon NM, Lavin C, Abbas D, Guardino N, Morgan A, Valencia C, Cotterell A, Longaker MT, and Wan DC

Abstract

Skin fibrosis is a clinical problem with devastating impacts but limited treatment options. In the setting of diabetes, insulin administration often causes local dermal fibrosis, leading to a range of clinical sequelae including impeded insulin absorption. Mechanical forces are important drivers of fibrosis and, clinically, physical tension offloading at the skin level using an elastomeric patch significantly reduces wound scarring. However, it is not known whether tension offloading could similarly prevent skin fibrosis in the setting of pro-fibrotic injections. Here, we develop a porcine model using repeated local injections of bleomycin to recapitulate key features of insulin-induced skin fibrosis. Using histologic, tissue ultrastructural, and biomechanical analyses, we show that application of a tension-offloading patch both prevents and rescues existing skin fibrosis from bleomycin injections. By applying single-cell transcriptomic analysis, we find that the fibrotic response to bleomycin involves shifts in myeloid cell dynamics from favoring putatively pro-regenerative to pro-fibrotic myeloid subtypes; in a mechanomodulatory in vitro platform, we show that these shifts are mechanically driven and reversed by exogenous IL4. Finally, using a human foreskin xenograft model, we show that IL4 treatment mitigates bleomycin-induced dermal fibrosis. Overall, this study highlights that skin tension offloading, using an FDA cleared, commercially available patch, could have significant potential clinical benefit for the millions of patients dependent on insulin., Competing Interests: COMPETING INTERESTS M.T.L. is a shareholder in Neodyne Biosciences, Inc., the company from which we purchased the embrace devices for this study but declares no non-financial competing interests. All other authors declare no financial or non-financial competing interests.

Published
2024
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30. Piezo inhibition prevents and rescues scarring by targeting the adipocyte to fibroblast transition.

Author

Griffin MF, Talbott HE, Guardino NJ, Guo JL, Spielman AF, Chen K, Parker JBL, Mascharak S, Henn D, Liang N, King M, Cotterell AC, Bauer-Rowe KE, Abbas DB, Diaz Deleon NM, Sivaraj D, Fahy EJ, Downer M, Akras D, Berry C, Cook J, Quarto N, Klein OD, Lorenz HP, Gurtner GC, Januszyk M, Wan DC, and Longaker MT

Abstract

While past studies have suggested that plasticity exists between dermal fibroblasts and adipocytes, it remains unknown whether fat actively contributes to fibrosis in scarring. We show that adipocytes convert to scar-forming fibroblasts in response to Piezo -mediated mechanosensing to drive wound fibrosis. We establish that mechanics alone are sufficient to drive adipocyte-to- fibroblast conversion. By leveraging clonal-lineage-tracing in combination with scRNA-seq, Visium, and CODEX, we define a "mechanically naïve" fibroblast-subpopulation that represents a transcriptionally intermediate state between adipocytes and scar-fibroblasts. Finally, we show that Piezo1 or Piezo2 -inhibition yields regenerative healing by preventing adipocytes' activation to fibroblasts, in both mouse-wounds and a novel human-xenograft-wound model. Importantly, Piezo1 -inhibition induced wound regeneration even in pre-existing established scars, a finding that suggests a role for adipocyte-to-fibroblast transition in wound remodeling, the least-understood phase of wound healing. Adipocyte-to-fibroblast transition may thus represent a therapeutic target for minimizing fibrosis via Piezo -inhibition in organs where fat contributes to fibrosis.

Published
2023
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