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Traumatized Muscle-Derived Multipotent Progenitor Cells: Pro-Angiogenic Activity, Promotion of Nerve Growth, and Osteogenic Differentiation

Hofer, Heidi R. (2015) Traumatized Muscle-Derived Multipotent Progenitor Cells: Pro-Angiogenic Activity, Promotion of Nerve Growth, and Osteogenic Differentiation. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Following trauma from high-energy blasts, a population of multipotent progenitor cells (MPCs) can be derived from the debrided muscle tissue. Given the non-intrusive nature of MPC isolation, MPCs represent an attractive clinical alternative to the more widely used mesenchymal stem cells derived from bone marrow and other tissue sources. This dissertation presents work which further defines the utility and limitations of MPCs in applications relevant to the repair of extremity injuries, including angiogenesis, peripheral nerve repair, and bone formation.
The secretome of MPCs enhanced in vitro angiogenesis, in a manner dependent on MPC production of vascular endothelial growth factor-A (VEGF). Encapsulated within mechanically tunable injectable hydrogel constructs, MPCs retained strong pro-angiogenic activity when implanted in vivo, supporting potential clinical use when enhanced vessel recruitment is desired.
Neurotrophically-induced MPCs, in combination with endothelial cells (ECs) co-cultured on aligned, nanofibrous scaffolds or via secretome interactions, supported neurite outgrowth and extension of chick embryonic dorsal root ganglia. These findings suggest that products of induced MPCs may be useful to enhance nerve guide conduit-based repair of peripheral nerves.
ECs influenced earlier and stronger MPC osteogenic gene expression, and IL-1β was associated with increased mineralization. The use of MPCs in bone replacement applications may thus result in mineralization without functional bone formation, depending on the level of inflammation at the site of construct implantation.
Taken together, this work extends the potential utility of MPCs for limb regenerative applications, especially for enhanced vessel or nerve recruitment. Caution must be exercised as MPCs may be influenced towards a mineralizing phenotype by the tissue environment, likely contributing to the heterotopic ossification pathology commonly seen following blast trauma.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Hofer, Heidi R.hrh7@pitt.eduHRH7
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairTuan, Rocky S.rst13@pitt.eduRST13
Committee MemberBanerjee, Ipsitaipb1@pitt.eduIPB1
Committee MemberMarra, Kaceymarrak@upmc.eduKGM5
Committee MemberRoy, Parthapar19@pitt.eduPAR19
Date: 9 June 2015
Date Type: Publication
Defense Date: 17 March 2015
Approval Date: 9 June 2015
Submission Date: 1 April 2015
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 146
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: MPCS; VEGF-A; bone marrow-derived MSCs; angiogenesis; synthetic nerve guide conduit; heterotopic ossification
Date Deposited: 09 Jun 2015 13:27
Last Modified: 19 Dec 2016 14:42


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