Low back pain is often related to intervertebral disc (IVD) degeneration that results from a progressive loss of proteoglycans and water content in the nucleus pulposus (NP). Autologous disc cell-based therapy is a promising approach for IVD regeneration. Unfortunately, the current in vitro expansion of NP cells in monolayer results in dedifferentiation of these cells. Synovium-derived stem cells (SDSCs) are tissue-specific stem cells for cartilage-like tissue regeneration. Our previous study indicates that SDSC-derived extracellular matrix (ECM) can provide a microenvironment for SDSC rejuvenation by enhancing proliferation capacity and chondrogenic differentiation potential. Since NP cells are chondrocyte-like cells, it is speculated that a more tissue-specific 3D microenvironment can maintain the phenotype of seeded NP cells during ex vivo expansion instead of standard 2D culture. Our most recent study suggests that such an in vitro 3D microenvironment benefits porcine NP cells by allowing them to expand more efficiently while maintaining their differentiation phenotypes. In this study, we hypothesize that decellularized matrix deposited by human SDSCs (hSDSCs) from fetal donors can serve as a tissue-specific high-quality microenvironment for ex vivo expansion of human NP cells from elderly patients while maintaining NP cell differentiated phenotype and re-differentiation potential.
Two specific aims will be performed: (1) comparison of expansion efficiency of human NP cells from herniated discs when grown on ECM deposited by hSDSCs from either fetal or adult donors;and (2) exploration of the underlying mechanism by evaluating global gene expression in human NP cells expanded on ECM from either fetal or adult donors using microarray analysis. Our long-term goal is to develop an autologous disc cell-based minimally invasive therapeutic approach toward physiological reconstruction of a biologically functional disc in a clinical setting.

Public Health Relevance

Autologous cell shortage is a big hurdle in clinical treatment of disc degeneration. Decellularized matrix deposited by tissue-specific stem cells provides a novel system for high-quality cell expansion. The aim of this study is to evaluate the feasibility f using tissue-specific matrix deposited by fetal synovial stem cells to expand human nucleus pulposus cells from elderly patients for disc regeneration.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Research Grants (R03)
Project #
1R03AR062763-01A1
Application #
8444166
Study Section
Special Emphasis Panel (ZAR1-EHB (M1))
Program Officer
Wang, Fei
Project Start
2013-06-01
Project End
2016-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$74,000
Indirect Cost
$24,000
Name
West Virginia University
Department
Orthopedics
Type
Schools of Medicine
DUNS #
191510239
City
Morgantown
State
WV
Country
United States
Zip Code
26506
Liu, Xiaozhen; Zhou, Long; Chen, Xi et al. (2016) Culturing on decellularized extracellular matrix enhances antioxidant properties of human umbilical cord-derived mesenchymal stem cells. Mater Sci Eng C Mater Biol Appl 61:437-48
Pizzute, Tyler; Zhang, Ying; He, Fan et al. (2016) Ascorbate-dependent impact on cell-derived matrix in modulation of stiffness and rejuvenation of infrapatellar fat derived stem cells toward chondrogenesis. Biomed Mater 11:045009
Zhang, Y; Chen, S; Pei, M (2016) Biomechanical signals guiding stem cell cartilage engineering: from molecular adaption to tissue functionality. Eur Cell Mater 31:59-78
Zhou, Long; Chen, Xi; Liu, Tao et al. (2015) Melatonin reverses H2 O2 -induced premature senescence in mesenchymal stem cells via the SIRT1-dependent pathway. J Pineal Res 59:190-205
Pizzute, Tyler; Lynch, Kevin; Pei, Ming (2015) Impact of tissue-specific stem cells on lineage-specific differentiation: a focus on the musculoskeletal system. Stem Cell Rev 11:119-32
Zhang, Ying; Pizzute, Tyler; Li, Jingting et al. (2015) sb203580 preconditioning recharges matrix-expanded human adult stem cells for chondrogenesis in an inflammatory environment - A feasible approach for autologous stem cell based osteoarthritic cartilage repair. Biomaterials 64:88-97
Chen, Song; Fu, Peiliang; Cong, Ruijun et al. (2015) Strategies to minimize hypertrophy in cartilage engineering and regeneration. Genes Dis 2:76-95
Zhang, Ying; Li, Jingting; Davis, Mary E et al. (2015) Delineation of in vitro chondrogenesis of human synovial stem cells following preconditioning using decellularized matrix. Acta Biomater 20:39-50
Lynch, Kevin; Pei, Ming (2014) Age associated communication between cells and matrix: a potential impact on stem cell-based tissue regeneration strategies. Organogenesis 10:289-98
Pei, Ming; Li, Jingting; Zhang, Ying et al. (2014) Expansion on a matrix deposited by nonchondrogenic urine stem cells strengthens the chondrogenic capacity of repeated-passage bone marrow stromal cells. Cell Tissue Res 356:391-403

Showing the most recent 10 out of 15 publications