Clinical Applications of Mesenchymal Stromal Cells 公开
Romanelli, Sarah (Fall 2020)
Published
Abstract
Mesenchymal stromal cells (MSCs) are multipotent progenitor cells which have been shown to exhibit immunomodulatory properties as well as to preferentially migrate to areas of upregulated immune response, such as tumors and sites of inflammation. When modified with the cytokine interferon gamma (IFN-γ), the immunomodulatory properties of MSCs can be enhanced. Therefore, MSCs present as an attractive candidate for cell therapy. Osteosarcoma is the most common malignant primary bone tumor in children and adolescents. Because metastatic, chemotherapy resistant, and relapsed osteosarcoma often results in poor prognoses, development of a targeted treatment is most crucial. The tumor microenvironment (TME) has been shown to be composed of various cellular components including tumor associated macrophages (TAMs), which exhibit different tumor proliferation effects based on their phenotype along an M1 to M2 continuum. With knowledge of MSCs migration to the tumor site and immunomodulatory properties, this study aims to use genetically modified MSCs as a targeted treatment delivery system for IFN-γ in order to increase anti-tumor M1 polarization. Future research aims to determine if delivery of MSCs transduced with IFN-γ can allow for an increased ratio of M1 to M2 macrophages in order to improve patient prognosis. Additionally, MSCs can be used for the treatment and prophylaxis of acute Graft-versus-Host Disease (aGvHD). aGvHD is a complication of blood and marrow transplantation in which donor T cells attack the patients’ healthy tissues. aGvHD is most effectively treated with glucocorticoids and various immunosuppressive drugs, however patients with steroid-resistant aGvHD often face poor prognosis. Therefore, this study aims to once again harness the migration of MSCs towards areas of high immunoactivity, such as activated T cells following transplantation. Consistent with our hypothesis, more MSCs were found in organs associated with the immune response, such as the spleen and mesenteric lymph nodes. It is hypothesized that increasing the immunosuppressive effects of MSCs via priming with IFN-γ will allow for the suppression of T cells and therefore reduced aGvHD. Through the lens of two different diseases, this study investigates the various clinical applications of MSCs.
Table of Contents
Introduction……………………………………………………………………………………… 8
Methodology……………………………………………………………………………………. 17
Results…………………………………………………………………………………………... 23
Discussion………………………………………………………………………………………. 30
Conclusion……………………………………………………………………………………… 33
References………………………………………………………………………………………. 37
Supplemental Methods……………………………………..……………………………….. 42
About this Honors Thesis
| School | |
|---|---|
| Department | |
| Degree | |
| Submission | |
| Language |
|
| Research Field | |
| 关键词 | |
| Committee Chair / Thesis Advisor | |
| Committee Members |
Primary PDF
| Thumbnail | Title | Date Uploaded | Actions |
|---|---|---|---|
|
|
Clinical Applications of Mesenchymal Stromal Cells () | 2020-12-18 13:21:57 -0500 |
|
Supplemental Files
| Thumbnail | Title | Date Uploaded | Actions |
|---|