Advanced Electrospinning Process : Energy : Healthcare : Environment

 

   

Stem cell research has the potential to benefit millions of people around the world requiring replacement or renewal of tissue function. Stem cells are unspecialized, multi-potential cells with the ability to self-renew indefinitely, and differentiate into more mature cells with specialized functions. The bone marrow contains at least two kinds of stem cells, the hematopoietic stem cells and bone marrow stromal cells (mesenchymal stem cells). An alternative source of hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) is human umbilical cord blood. Hematopoietic stem cells give rise to all the types of blood cells: red blood cells, B lymphocytes, T lymphocytes, natural killer cells, neutrophils, basophils, eosinophils, monocytes, macrophages, and platelets. Mesenchymal stem cells give rise to a variety of cell types: bone cells (osteocytes), cartilage cells (chondrocytes), fat cells (adipocytes) and other kinds of connective tissue cells such as those in tendons. Since the population percentage of stem cells is small, the capture and expansion of stem cells is essential in order to propagate sufficient cells for research, clinical and biomedical applications and tissue engineering.

We have shown that functionalized random, aligned and core-shell nanofiber mats support the adhesion and proliferation of endothelial and smooth muscle cells for blood vessels, fibroblasts for dermal substitution, osteoblasts for bone regeneration, hepatocytes for potential liver regeneration, and neural stem cells for nerve regeneration. We have been able to expand CD34+ hematopoietic stem cells on animated PCL nanofiber mesh for hematological malignancies, and capture human mesenchymal stem cells using collagen nanofiber scaffolds for bone implantation. The core-shell nanofibers developed in our laboratory can be used to encapsulate growth factors and bioactive molecules to further enhance the biomimetic properties of the scaffolds. Release kinetic studies of core-shell nanofibers encapsulating fluorescein isothiocyanate conjugated bovine serum albumin (FITC-BSA) cultured with/without human dermal fibroblasts (HDFs) has shown a gradual release of FITC-BSA instead of a burst release profile. This release profile is crucial for regulating cell growth if the nanofiber scaffolds for tissue engineering applications are to encapsulate bioactive molecules.

The proposed research aims for the expansion of the hematopoietic stem cells (CD34+) using functionalized nanofibers for the management of hematological malignancies, breast cancer, thalassemia, sickle cell diseases and aplastic anemia. Work in our laboratory on cell adhesion, co-culture and cell proliferation on nanofiber scaffolds has demonstrated that nanofibers can provide a conducive environment for stem cell capture and expansion. The hypothesis is that the modified nanofiber mesh architecture provides a unique microenvironment to facilitate the expansion of hematopoietic and mesenchymal stem cells. The research is also targeted at the capture and expansion of mesenchymal stem cells, elucidating some of the molecular mechanisms underlying mesenchymal stem cell differentiation into chondrocytes, osteocytes, osteoblasts, vascular endothelial cells, smooth muscle cells, neuronal stem cells, and fibroblasts, and the key environmental triggers determining these cascades, notably: growth factors and mechanical stimuli, including shear stress, disturbed flow, uniaxial and biaxial stretching using functionalized electrospun nanofibers (aligned, random and core-shell nanofibers) as a model system. The goal is to understand the sensing of mechanical cues and the link to modulated gene expression and eventually cellular function.

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