The synergistic effect of NOTCH, SALL4, and hydrogel on hematopoietic stem cells

描述（由申请人提供）：造血干细胞（hsc）是一种罕见的干细胞，具有分化为特化血细胞的能力，包括淋巴细胞、红细胞和血小板。造血干细胞在临床移植方案中用于治疗各种疾病，包括白血病、先天性血液和免疫系统异常、再生障碍性贫血和血红蛋白病。然而，寻找匹配的捐赠者是困难的，耗时的，特别是对非洲裔美国人，西班牙裔美国人，美洲原住民和混合种族的人来说。目前，只有三分之一的患者能找到合适的供体；因此，许多患者在找到合适的配型之前就去世了。虽然在过去的三十年里，研究人员已经成功地扩增了这些细胞，但仍然没有一种常规的体外扩增人造血干细胞的方法，并且在临床应用中取得了有限的成功。

DESCRIPTION (provided by applicant): Hematopoietic stem cells (HSCs) are rare stem cells that have the ability to differentiate into specialized blood cells, including lymphocytes, red blod cells, and platelets. HSCs are used in clinical transplantation protocols to treat a variety of diseases, including leukemia, inborn anomalies of the blood and immune system, aplastic anemia, and hemoglobinopathies. However, finding a matching donor is difficult, time consuming, and especially problematic for African Americans, Hispanics, Native Americans, and people of mixed ethnicity. Currently, only 1 in 3 patients will find a suitable donor; thus, many patients die before finding an appropriate match. While studies to successfully expand these cells have spanned over the last three decades, a routine method for ex vivo expansion of human HSCs is still not available and has been met with limited success for clinical applications. We hypothesize that both intrinsic and extrinsic factors play key roles in obtaining a suitable population of HSCs/HPCs (hematopoietic progenitor cells) for successful bone marrow transplantation. If successful, the proposed innovative approach has the potential to transform the field of bone marrow transplantation, and offers a curative option for patients with a wide spectrum of diseases including hematologic cancers, immune deficiency disorders, and aplastic anemia. The Specific Aims of our proposal are focused on achieving this objective. Aim 1. To determine if there is a synergistic effect between ICD-NOTCH and a hydrogel extracellular matrix in promoting definitive HSC/HPC expansion of human umbilical cord blood (hUCB). Aim 2. To compare if expansion approaches of hUCB that utilize ICD-NOTCH, SALL4, and a hydrogel extracellular matrix in combination will promote higher efficiency of short- term and long-term repopulation to marrow recovery.