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Environment And Response Of 3d-Encapsulated Mesenchymal Stem Cells To Mechanical Loading, Augustus Greenwood

McKelvey School of Engineering Theses & Dissertations

This thesis explores the micromechanical environment induced when cyclically compressing hydrogels via finite element modeling and experimentally on the impact of loading on mesenchymal stem cells (MSCs) when encapsulated withing 3D hydrogel matrices. Degenerative joint diseases, characterized by cartilage degradation, present significant challenges due to cartilage's limited self-repair capacity. Innovative approaches, including stem cell-based therapies and engineered biomaterials, have emerged as promising strategies for cartilage repair and regeneration. This work specifically investigates the calibration of a bioreactor, the uniformity of load response across the hydrogel constructs via finite element modeling (FEM), and the stress response of MSCs subjected to various …

Evaluation Of Mesenchymal Stem Cells In Autoimmune Disease: A Systematic Review And Meta-Analysis, Hailey Nicole Swain

Masters Theses

"Mesenchymal stem cells, also known as multipotential stem/progenitor cells and mesenchymal stem/progenitor cells, are denoted by the acronym MSCs. MSCs can differentiate into multiple lineages from different germ layers in vitro, and in limited situations, in vivo. MSCs have broad anti-inflammatory and immune-modulatory properties, which is the greatest focus of MSCs in clinical testing. Despite their promise and use in over 950 clinical trials, pivotal questions remain unanswered. Recent clinical trials have demonstrated that when MSCs are harvested from autoimmune patients, they show a reduction in their therapeutic efficacy in comparison to MSCs from a healthy person. Identifying quality MSCs …

A Protein-Based Therapeutic Combination For The Treatment Of Hard-To-Heal Wounds, Graham L. Strauss

USF Tampa Graduate Theses and Dissertations

Chronic wounds present many clinical challenges in relation to the successful treatment and closure of the damaged tissue. Most current treatment methods focused on one or two aspects to drive wound closure, while most chronic wounds are multifactorial environments with many of those dependencies relying on the termination of one another to effectively gain tissue construction, closure, and full skin thickness and composition. Natural wound healing processes allude to potential biologics that can impede the chronic breakdown of tissue, while restoring deposition of new tissue, and effectively leading to a healed wound. Proteases secreted by the body’s immune system lay …

Donor Age Effects On The Proliferative And Chondrogenic/Osteogenic Differentiation Performance Of Equine Bone Marrow- And Adipose Tissue Derived Mesenchymal Stem Cells In Culture, Jasmin Bagge

Theses and Dissertations--Veterinary Science

Orthopedic injuries are a major cause of lameness and morbidity in horses. Bone marrow (BM)- and adipose tissue (AT) derived mesenchymal stem cells (MSCs) have shown potential to facilitate the repair of orthopedic injuries and are being used increasingly in veterinary clinics. Presently, the use of MSCs as a therapy for equine patients is most commonly applied as autologous transplants, using BM- and AT-MSCs harvested from the patient shortly after the time of injury. Cell-based therapies are therefore delayed to enable primary cell numbers to be expanded in culture. Of concern, however, are human and rodent studies that have shown …

Novel Osteobiologics For Bone Tissue Engineering, Austin Bow

Doctoral Dissertations

The field of bone tissue engineering features a wide variety of biomaterials designed to facilitate repair and restoration of injured bone tissue. Due to the complex nature of bone, these graft materials face unique challenges in accommodating this highly dynamic environment in which internal structures are being constantly remodeled via osteoblastic and osteoclastic functions. Therefore, effective graft designs must incorporate compositional elements that are capable of promoting and facilitating such activity to permit successful integration with native tissue. These osteobiologic characteristics, including osteo-conduction, osteo-induction, and osseo-integration, are key factors in determining a materials osteogenic capacity and its potential as a …

The Role Of Pannexin 1 During Human Adipogenesis In Vitro, Jamie Emily Ching

Electronic Thesis and Dissertation Repository

Obesity is the unhealthy accumulation of adipose tissue and affects 10% of the global population. A study reported the loss of mouse pannexin 1 (Panx1), a large channel forming protein, increased adipogenesis in murine adipose derived stem cells (ASCs). Our study was designed to determine if human pannexin 1 (PANX1) inhibits adipogenesis in vitro using human ASCs and induced-mesenchymal stem cells (iMSCs) derived from induced pluripotent stem cells (iPSCs). Pharmacological inhibition of PANX1 using carbenoxolone halted adipogenesis in both the ASCs and iMSCs. When PANX1 was inhibited by probenecid, adipogenesis was impeded in iMSCs, but not in ASCs. PANX1-ablated iPSCs …

Graphene-Based Nanomaterials In The Design Of Nerve Conduits For Regenerative Medicine Applications, Richard Steiner

Doctoral Dissertations

Peripheral neuropathies are a debilitating problem in human and animal patients resulting in a diminished quality of life. The current gold standard methods for repair of critical size peripheral neuropathies have limitations that overall diminish the quality of life for patients. The use of nerve scaffolds composed of synthetic polymer-based materials to heal damaged nerves has become an attractive approach in regenerative medicine research. Studies have shown the biomaterial characteristics of graphene oxide to have potential in applications for regenerating damaged peripheral nerves. Studies have also shown that incorporating Mesenchymal Stem Cell (MSC) therapies into neural scaffold designs can significantly …

Characterization Of Hybrid Synthetic/Adipose-Derived Ecm Scaffolds, John Nicholas Poche

LSU Master's Theses

Evolving out of a need to address growing concerns regarding current methods of tissue transplantation, the field of tissue engineering seeks to facilitate the regeneration of viable tissue through the use of cellular scaffolds. The first aim of this thesis was to provide a summary of the current literature on advances in biomaterial synthesis and pertaining methods of stem cell delivery in tissue engineering. Improvements in the processing of decellularized tissue and the expansion of synthetic hydrogels as platforms for stem cell encapsulation have led to the development of extracellular matrix (ECM)-based hybrid hydrogels. These stem cell scaffolds are currently …

Characterization Of Biopolymeric Micro- Nano Structured 3d Porous Matrices In Combination With Bone Marrow Derived Mesenchymal Stem Cells For Bone Regeneration, Aja Aravamudhan

Doctoral Dissertations

Archival abstract submitted

Development And Characterization Of Lung Derived Extracellular Matrix Hydrogels, Robert A. Pouliot

Theses and Dissertations

Chronic obstructive pulmonary disease (COPD) including emphysema is a devastating condition, increasing in prevalence in the US and worldwide. There remains no cure for COPD, rather only symptomatic treatments. Due to unique challenges of the lung, translation of therapies for acute lung injury to target chronic lung diseases like COPD has not been successful. We have been investigating lung derived extracellular matrix (ECM) hydrogels as a novel approach for delivery of cellular therapies to the pulmonary system.

During the course of this work we have developed and characterized a lug derived ECM hydrogel that exhibits “injectability,” allowing cells or dugs …

Polymeric Nanocarriers For Treatment Of Melanoma And Genetically Modified Mesenchymal Stem Cells To Improve Outcome Of Islet Transplantation, Vaibhav Mundra

Theses & Dissertations

Melanoma is a lethal malignancy with limited treatment options for advanced metastatic stages. New targeted therapeutic options with discovery of BRAF and MEK inhibitors have shown significant survival benefit. Despite the recent progress, inefficient tumor accumulation and dose limiting systemic toxicity remains pressing challenges for treating metastatic melanoma and there is a need for drug delivery approach to improve therapeutic index of chemotherapeutics. Nanoparticle based drug delivery represents promising approach to enhance efficacy and reduce the dose limiting systemic toxicity. Nanoparticles can be formulated either by physical encapsulation of drugs or by covalent conjugation of drugs to the polymeric backbone. …

S-Nitrosoglutathione Reductase-Dependent Ppargamma Denitrosylation Participates In Msc-Derived Adipogenesis And Osteogenesis, Yenong Cao

Open Access Dissertations

Osteogenesis and adipogenesis are two closely linked processes that share the same precursor, bone marrow mesenchymal stem cells (MSCs). MSCs are a rare population of non-hematopoietic stromal cells, present in bone marrow and almost every type of connective tissue. It is crucial to understand the signals that govern the specificity of MSC differentiation. Adipogenic transcription factor PPARγ can stimulate adipogenesis while inhibit osteogenesis. However, the role of potential regulators of PPARγ activity in this differentiation shift remains unknown. One potential regulator is nitric oxide (NO). NO enhances adipogenesis of human preadipocytes while decreasing cell proliferation. Studies in mice with a …

Development Of Scaffold Architectures And Heterotypic Cell Systems For Hepatocyte Transplantation, Dalia Alzebdeh

Wayne State University Dissertations

In vitro assembly of functional liver tissue is needed to enable the transplantation of tissue-engineered livers. In addition, there is an increasing demand for in vitro models that replicate complex events occurring in the liver. However, tissue engineering of sizable implantable liver systems is currently limited by the difficulty of assembling three dimensional hepatocyte cultures of a useful size, while maintaining full cell viability, an issue which is closely related to the high metabolic rate of hepatocytes. In this study, we first compared two designs of highly porous chitosan-heparin scaffolds seeded with hepatocytes in dynamic perfusion bioreactor systems. The aim …

The Effects Of Nicotine On Mesenchymal Stem Cell Function, Carlos M. Carballosa

Open Access Theses

This research focuses on the effects nicotine exposure has on Human, Bone Marrow Derived Mesenchymal Stem Cell (MSC) proliferation, migration and differentiation potential. Nicotine, the quintessential compound responsible for a smoker’s addiction to cigarettes, is an organic compound, whose effects are either positive or negative depending on the dose of nicotine metabolized. In low concentrations, nicotine has been shown to induce angiogenesis and improve diseases such as Alzheimer’s and Parkinson’s. In high doses, however, nicotine has been shown to have detrimental effects including hindering both embryonic stem cell development and skeletal healing. Although much has been discovered about the effects …

Effects Of Mild Heating On The Osteogenic Differentiation Of Human Mesenchymal Stem Cells During Inflammation, Kristifor Sunderic

Dissertations and Theses

"Current surgical procedures to treat osteoarthritis have varying degrees of success, but carry inherent risks and a finite life expectancy. A more permanent solution is a treatment that regenerates biologically viable tissue that integrates with the patient and retains functionality. For maximal effectiveness, such a treatment should also repair bone loss known to occur in osteoarthritis and attenuate chronic inflammation that can obstruct healing. Mesenchymal stem cells have great potential to be used as part of a novel therapy for bone and cartilage regeneration. They are a highly regulated, self-renewing population of cells with potent mechanisms to avoid allogeneic rejection, …

Reinforced Chitosan-Based Heart Valve Scaffold And Utility Of Bone Marrow-Derived Mesenchymal Stem Cells For Cardiovascular Tissue Engineering, Mohammad Z. Albanna

Wayne State University Dissertations

Recent research has demonstrated a strong correlation between the differentiation profile of mesenchymal stem cells (MSCs) and scaffold stiffness. Chitosan is being widely studied for tissue engineering applications due to its biocompatibility and biodegradability. However, its use in load-bearing applications is limited due to moderate to low mechanical properties. In this study, we investigated the effectiveness of a fiber reinforcement method for enhancing the mechanical properties of chitosan scaffolds. Chitosan fibers were fabricated using a solution extrusion and neutralization method and incorporated into porous chitosan scaffolds. The effects of different fiber/scaffold mass ratios, fiber mechanical properties and fiber lengths on …

Rac1b Regulates The Neurotrophin-3 Mediated Neuronal Commitment Of Bone Marrow Derived Miami Cells, Kevin M. Curtis

Open Access Dissertations

Emerging trends in cell-therapy based tissue repair have focused on the renewable source of adult stem cells including human bone marrow-derived mesenchymal stromal cells (hMSCs). Due to immunomodulatory properties as well as a potential to differentiate into cells characteristic of all three germ layers, hMSCs provide a source of immature cells for utilization in cell-therapy based treatments. Marrow isolated adult multilineage inducible (MIAMI) cells are a homogeneous sub-population of hMSCs which maintain self-renewal potential during ex vivo expansion, in addition to efficiently undergoing trans-differentiation into neuron-like cells in vitro. Even though hMSCs have the potential to be used for neural …

The Development Of A Mesenchymal Stem Cell Based Biphasic Osteochondral Tissue Engineered Construct, Scott Maxson

All Dissertations

The ability of human articular cartilage to respond to injury is poor. Once cartilage damage has occurred, an irreversible degenerative process can occur and will often lead to osteoarthritis (OA). An estimated 26.9 million of U.S. adults are affected by OA. Osteochondral grafting is currently used to treat OA and osteochondral defects; however, complications can develop at the donor site and defect area. Osteochondral tissue engineering provides a potential treatment option and alternative to osteochondral grafting. The long term goal of this work is to develop a tissue engineered mesenchymal stem cell (MSC) based osteochondral construct to repair cartilage damage. …

The Development Of A Mesenchymal Stem Cell Based Bone Graft System, Sarina Sinclair

All Dissertations

Greater than 5.5 million fractures are sustained by Americans each year, accounting for more than 500,000 bone graft surgeries. Bone grafts are the second most transplanted material, surpassed only by blood. The current 'gold standard' for bone grafting involves harvesting bone material from the patient's iliac crest, due to its osteoinductive properties. Unfortunately, the surgery required to harvest material from the iliac crest causes additional pain for the patient, relies on a limited amount of available bone tissue, and results in, on average, a 30% rate of donor site morbidity. Both natural and synthetic substitutes have been developed to avoid …