The effects of a pro-angiogenic, RGD-functionalized, nanofiber composite biomaterial on mesenchymal stem cell-mediated repair of the injured spinal cord

Agnes Haggerty PhD

Abstract:

Spinal cord injury (SCI) results in nervous tissue loss and so far untreatable functional impairments. Preclinical studies have demonstrated that a transplant of bone marrow-derived mesenchymal stem cells (MSCs) elicits paracrine effects resulting in anatomical repair and partial functional recovery. The effects of transplanted MSCs on spinal cord repair depend on their survival. MSCs are anchorage-dependent cells that are susceptible to anoikis, i.e., programmed cell death due to lack of adherence to a substrate. Thus, MSC transplant-mediated repair may be affected by lack of a binding substrate. It is known that MSCs adhere via integrin receptors to the tripeptide, arginine-glycine-aspartic acid (RGD). We investigated the effects of an RGD-functionalized nanofiber hydrogel composite biomaterial (NHC) on MSC transplant survival and the effects on anatomical repair and functional recovery in a clinically relevant adult rat model of spinal cord contusion. NHC consists of pro-angiogenic hyaluronic acid and axon growth-promoting nanofibers which form an injectable composite gel that closely resembles the physical properties (i.e. stiffness/porosity) of the spinal cord nervous tissue. NHC could target a multitude of factors that influencing MSC transplant survival and tissue remodeling after SCI. Pilot data suggests NHC improves MSC transplant survival and anatomical repair of the damaged spinal cord.

Authors*A. E. HAGGERTY¹, X. LI³, Y. NITOBE^1,4, I. MALDONADO-LASUNCION^1,5, K. YAMANE^1,6, M. MARLOW¹, H.-Q. MAO³, M. OUDEGA^2,7,8,1;
¹The Miami Project, ²Dept. of Neurolog. Surgery, Univ. of Miami, Miami, FL; ³Materials Sci. and Engineering, Inst. for NanoBiotechnology, Johns Hopkins Univ., Baltimore, MD; ⁴Dept. of Orthopedic Surgery, Hirosaki Univ. Grad. Sch. of Med., Hirosaki, Japan; ⁵Netherlands Inst. for Neurosciences, Amsterdam, Netherlands; ⁶Dept. of Orthopedic Surgery, Okayama Univ., Okayama, Japan; ⁷Affiliated Cancer Hosp. and Inst., Guangzhou Med. Univ., Guangzhou, China; ⁸Bruce W. Carter Dept. of Veterans Affairs Med. Ctr., Miami, FL

Disclosures A.E. Haggerty: None. X. Li: None. Y. Nitobe: None. I. Maldonado-Lasuncion: None. K. Yamane:None. M. Marlow: None. H. Mao: None. M. Oudega: None.

This work is supported by the Miami Project, State of Florida, Maryland Stem Cell Research Fund (2018-MSCRFCO-4088), and Department of Veteran Affairs (I01BX007080).

Program No. 213.21. 2018 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2018. Online.

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