skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: Bioengineering Cell Therapy for Treatment of Peripheral Artery Disease
Peripheral artery disease is an atherosclerotic disease associated with limb ischemia that necessitates limb amputation in severe cases. Cell therapies comprised of adult mononuclear or stromal cells have been clinically tested and show moderate benefits. Bioengineering strategies can be applied to modify cell behavior and function in a controllable fashion. Using mechanically tunable or spatially controllable biomaterials, we highlight examples in which biomaterials can increase the survival and function of the transplanted cells to improve their revascularization efficacy in preclinical models. Biomaterials can be used in conjunction with soluble factors or genetic approaches to further modulate the behavior of transplanted cells and the locally implanted tissue environment in vivo. We critically assess the advances in bioengineering strategies such as 3-dimensional bioprinting and immunomodulatory biomaterials that can be applied to the treatment of peripheral artery disease and then discuss the current challenges and future directions in the implementation of bioengineering strategies.  more » « less
Award ID(s):
2227614
PAR ID:
10562824
Author(s) / Creator(s):
; ; ; ; ;
Publisher / Repository:
John Wiley & Sons
Date Published:
Journal Name:
Arteriosclerosis, Thrombosis, and Vascular Biology
Volume:
44
Issue:
3
ISSN:
1079-5642
Subject(s) / Keyword(s):
atherosclerosis peripheral arterial disease critical limb threatening ischemia cell therapy angiogenesis
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract Bioengineering and regenerative medicine strategies are promising for the treatment of vascular diseases. However, current limitations inhibit the ability of these approaches to be translated to clinical practice. Here we summarize some of the big bottlenecks that inhibit vascular regeneration in the disease applications of aortic aneurysms, stroke, and peripheral artery disease. We also describe the bottlenecks preventing three-dimensional bioprinting of vascular networks for tissue engineering applications. Finally, we describe emerging technologies and opportunities to overcome these challenges to advance vascular regeneration. 
    more » « less
  2. Jane E. Freedman (Ed.)
    Peripheral artery disease (PAD) affects 10 million people in the United States and >230 million worldwide.1,2 It is associated with impaired vascular perfusion to the lower extremities, leading to limbthreatening amputation in severe cases of critical limb ischemia. Patients with PAD have an inferior prognosis and reduced limb function, when compared with patients without PAD.3 Very few effective therapies have been identified, in part, because the key biologic pathways associated with functional impairment remain unclear. Current treatments include supervised and home-based walking exercise to improve the mobility in patients with PAD.4,5 A better understanding of the underlying pathological mechanisms of skeletal muscle damage underlying PAD may help identify new therapeutic opportunities 
    more » « less
  3. The parathyroid cell is a vital regulator of extracellular calcium levels, operating through the secretion of parathyroid hormone (PTH). Despite its importance, the regulation of PTH secretion remains complex and not fully understood, representing a unique interplay between extracellular and intracellular calcium, and hormone secretion. One significant challenge in parathyroid research has been the difficulty in maintaining cells ex vivo for in-depth cellular investigations. To address this issue, we introduce a novel platform for parathyroid cell transplantation and noninvasive in vivo imaging using the anterior chamber of the eye as a transplantation site. We found that parathyroid adenoma tissue transplanted into the mouse eye engrafted onto the iris, became vascularized, and retained cellular composition. Transplanted animals exhibited elevated PTH levels, indicating a functional graft. With in vivo confocal microscopy, we were able to repetitively monitor parathyroid graft morphology and vascularization. In summary, there is a pressing need for new methods to study complex cellular processes in parathyroid cells. Our study provides a novel approach for noninvasive in vivo investigations that can be applied to understand parathyroid physiology and pathology under physiological and pathological conditions. This innovative strategy can deepen our knowledge on parathyroid function and disease. 
    more » « less
  4. Millions of adults are affected by progressive vision loss worldwide. The rising incidence of retinal diseases can be attributed to damage or degeneration of neurons that convert light into electrical signals for vision. Contemporary cell replacement therapies have transplanted stem and progenitor-like cells (SCs) into adult retinal tissue to replace damaged neurons and restore the visual neural network. However, the inability of SCs to migrate to targeted areas remains a fundamental challenge. Current bioengineering projects aim to integrate microfluidic technologies with organotypic cultures to examine SC behaviors within biomimetic environments. The application of neural phantoms, or eye facsimiles, in such systems will greatly aid the study of SC migratory behaviors in 3D. This project developed a bioengineering system, called the μ-Eye, to stimulate and examine the migration of retinal SCs within eye facsimiles using external chemical and electrical stimuli. Results illustrate that the imposed fields stimulated large, directional SC migration into eye facsimiles, and that electro-chemotactic stimuli produced significantly larger increases in cell migration than the individual stimuli combined. These findings highlight the significance of microfluidic systems in the development of approaches that apply external fields for neural repair and promote migration-targeted strategies for retinal cell replacement therapy. 
    more » « less
  5. Regenerative retinal therapies have introduced progenitor cells to replace dysfunctional or injured neurons and regain visual function. While contemporary cell replacement therapies have delivered retinal progenitor cells (RPCs) within customized biomaterials to promote viability and enable transplantation, outcomes have been severely limited by the misdirected and/or insufficient migration of transplanted cells. RPCs must achieve appropriate spatial and functional positioning in host retina, collectively, to restore vision, whereas movement of clustered cells differs substantially from the single cell migration studied in classical chemotaxis models. Defining how RPCs interact with each other, neighboring cell types and surrounding extracellular matrixes are critical to our understanding of retinogenesis and the development of effective, cell-based approaches to retinal replacement. The current article describes a new bio-engineering approach to investigate the migratory responses of innate collections of RPCs upon extracellular substrates by combining microfluidics with the well-established invertebrate model of Drosophila melanogaster. Experiments utilized microfluidics to investigate how the composition, size, and adhesion of RPC clusters on defined extracellular substrates affected migration to exogenous chemotactic signaling. Results demonstrated that retinal cluster size and composition influenced RPC clustering upon extracellular substrates of concanavalin (Con-A), Laminin (LM), and poly-L-lysine (PLL), and that RPC cluster size greatly altered collective migratory responses to signaling from Fibroblast Growth Factor (FGF), a primary chemotactic agent in Drosophila. These results highlight the significance of examining collective cell-biomaterial interactions on bio-substrates of emerging biomaterials to aid directional migration of transplanted cells. Our approach further introduces the benefits of pairing genetically controlled models with experimentally controlled microenvironments to advance cell replacement therapies. 
    more » « less