Low back pain causes severe morbidity and imposes high socioeconomic burden. Degeneration of the intervertebral disc (IVD) is one of the common causes for low back pain. Cell therapy is an emerging solution to restore cellularity and functionality of the nucleus pulposus (NP) of the IVD, with potential to reverse disc degeneration or regenerate the disc. Due to poor availability, neither autologous notochordal cells nor mature NP cells are a clinically viable sources for NP regeneration. Our preliminary data showed that viable notochordal-like cells can be generated from human induced pluripotent stem cells (Liu et al. J Biomed Mater Res 2014; Liu et al. PLoS One 2014). In a stepwise manner, we coaxed iPSCs first to acquire a notochordal-like phenotype by co-expressing brachyury, cytokeratin-8 and -18 (T+/CK8+/CK18+), and then to a mature NP- like phenotype expressing SOX9, aggrecan and collagen type II, and elaborating a native-like matrix with characteristic high ratio of proteoglycan: collagen content. Based on our preliminary data, we hypothesize that human pluripotent stem cells-derived notochordal-like cells are viable progenitors for NP regeneration and yield native-like NP tissue. A central goal of this SBIR Phase I proposal is to develop a xeno-free protocol based on our existing one, and further determine the efficacy and safety of the derived notochordal-like cells in vivo. Outcome of this SBIR Phase I will establish the feasibility of a previously untapped cell source for NP regeneration, complementary to the existing work using hyaline chondrocytes and mesenchymal stromal cells.

Public Health Relevance

Low back pain causes severe morbidity and imposes high socioeconomic burden. Degeneration of the intervertebral disc (IVD) is one of the common causes for low back pain. We will develop a technology from the human pluripotent stem cells that regenerate a part of the IVD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43AR071194-01
Application #
9255083
Study Section
Special Emphasis Panel (ZRG1-MOSS-D (10)B)
Program Officer
Wang, Xibin
Project Start
2016-09-20
Project End
2017-02-28
Budget Start
2016-09-20
Budget End
2017-02-28
Support Year
1
Fiscal Year
2016
Total Cost
$225,000
Indirect Cost
Name
Innovative Elements, LLC
Department
Type
DUNS #
809512853
City
Englewood Cliffs
State
NJ
Country
United States
Zip Code
07632