Immune-responsive biodegradable scaffolds for enhancing neutrophil regeneration
| Autor: | Kerr, Matthew D, McBride, David A, Johnson, Wade T, Chumber, Arun K, Najibi, Alexander J, Seo, Bo Ri, Stafford, Alexander G, Scadden, David T, Mooney, David J, Shah, Nisarg J |
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| Rok vydání: | 2022 |
| Předmět: |
Transplantation
neutrophils 5.2 Cellular and gene therapies Inflammatory and immune system Stem Cell Research - Nonembryonic - Non-Human Hematology Development of treatments and therapeutic interventions hematopoietic stem cell transplant Regenerative Medicine Stem Cell Research immunodeficiency biomaterials |
| Zdroj: | Bioengineering & translational medicine, vol 8, iss 1 |
| DOI: | 10.1101/2022.01.21.477275 |
| Popis: | Neutrophils are essential effector cells for mediating rapid host defense and their insufficiency arising from therapy-induced side-effects, termed neutropenia, can lead to immunodeficiency-associated complications. In autologous hematopoietic stem cell transplantation (HSCT), neutropenia is a complication that limits therapeutic efficacy. Here, we report the development and in vivo evaluation of an injectable, biodegradable hyaluronic acid (HA)-based scaffold, termed HA cryogel, with myeloid responsive degradation behavior. In mouse models of immune deficiency, we show that the infiltration of functional myeloid-lineage cells, specifically neutrophils, is essential to mediate HA cryogel degradation. Post-HSCT neutropenia in recipient mice delayed degradation of HA cryogels by up to 3 weeks. We harnessed the neutrophil-responsive degradation to sustain the release of granulocyte colony stimulating factor (G-CSF) from HA cryogels. Sustained release of G-CSF from HA cryogels enhanced post-HSCT neutrophil recovery, comparable to pegylated G-CSF, which, in turn, accelerated cryogel degradation. HA cryogels are a potential approach for enhancing neutrophils and concurrently assessing immune recovery in neutropenic hosts. |
| Databáze: | OpenAIRE |
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