An Injectable Hyaluronan–Methylcellulose (HAMC) Hydrogel Combined with Wharton’s Jelly-Derived Mesenchymal Stromal Cells (WJ-MSCs) Promotes Degenerative Disc Repair

Abstract

Intervertebral disc (IVD) degeneration is one of the predominant causes of chronic low back pain (LBP), which is a leading cause of disability worldwide. Despite substantial progress in cell therapy for the treatment of IVD degeneration, significant challenges remain for clinical application. Here, we investigated the effectiveness of hyaluronan–methylcellulose (HAMC) hydrogels loaded with Wharton’s Jelly-derived mesenchymal stromal cell (WJ-MSCs) in vitro and in a rat coccygeal IVD degeneration model. Following induction of injury-induced IVD degeneration, female Sprague-Dawley rats were randomized into four groups to undergo a single intradiscal injection of the following: (1) phosphate buffered saline (PBS) vehicle, (2) HAMC, (3) WJ-MSCs (2 × 104 cells), and (4) WJ-MSCs-loaded HAMC (WJ-MSCs/HAMC) (n = 10/each group). Coccygeal discs were removed following sacrifice 6 weeks after implantation for radiologic and histologic analysis. We confirmed previous findings that encapsulation in HAMC increases the viability of WJ-MSCs for disc repair. The HAMC gel maintained significant cell viability in vitro. In addition, combined implantation of WJ-MSCs and HAMC significantly promoted degenerative disc repair compared to WJ-MSCs alone, presumably by improving nucleus pulposus cells viability and decreasing extracellular matrix degradation. Our results suggest that WJ-MSCs-loaded HAMC promotes IVD repair more effectively than cell injection alone and supports the potential clinical use of HAMC for cell delivery to arrest IVD degeneration or to promote IVD regeneration.

Decellularized Disc Hydrogels for hBMSCs tissue-specific differentiation and tissue regeneration

“…Biomaterials for NP replacement have focused mainly on injectable synthetic or biologically based hydrogels [ [7] , [8] , [9] ]. These hydrogels are mainly derived from non-degradable polyacrylates and polyacrylamides [ 10 , 11 ] and degradable hyaluronic acid, collagen in the extracellular matrix and chitosan [ 8 , 12 ]. However, these implanted materials often failed to regulate the post-injury microenvironment, and tissue degeneration, water loss and inflammatory reaction often appeared in situ [ 13 , 14 ].…”

Safety and efficacy of Wharton's jelly-derived mesenchymal stem cells with teriparatide for osteoporotic vertebral fractures: A phase I/IIa study

“…WJ‐MSCs express low levels of human leukocyte antigen (HLA) class I and no HLA‐DR leading to low immunogenicity. Additionally, WJ‐MSCs bear better immunomodulatory potential and anti‐inflammatory effects by suppressing mitogen‐induced T‐cell responses to a greater extent than MSCs from either bone marrow or adipose tissue 31 . In this study, the control group received only teriparatide (subcutaneous, 6 months, PTH), and the experimental treatment group received teriparatide (subcutaneous, 6 months) and stem cell injections (intramedullary injection of WJ‐MSCs [direct injection into the recently fractured vertebra] at baseline and intravenous injection at 7 days after intramedullary injection).…”

Genetic Therapy for Intervertebral Disc Degeneration

“…In this process, mesenchymal stem cells (MSCs) isolated from bone marrow, adipose tissue, umbilical cord Wharton’s jelly, and synovial membrane have been used due to their self-renewal capacity, anti-inflammatory properties, and their ability to regenerate degenerated disc cells [ 43 , 44 , 45 ]. The mechanism of stem cell therapy has been reported to have a paracrine effect (anti-inflammatory, anti-apoptotic), be capable of the restoration of degenerated discs, and initiate differentiation of implanted stem cells into NP cells [ 3 , 4 , 5 , 6 , 7 , 8 , 46 ].…”

“…For mild and moderate IVDD, stem cell transplantation may be an effective treatment. However, for severe IVDD that requires structural support, multifunctional treatment is possible through tissue engineering [ 4 , 5 , 6 , 7 , 8 , 46 ].…”

“…The intervertebral disc (IVD) is made of fibrous cartilage and is the most important functional part of the spine, presenting in between the vertebral bones providing flexibility to the vertebrae. It consists of the nucleus pulposus (NP), surrounded by the annulus fibrosus (AF), and the cartilaginous endplate [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. NP cells are similar to chondrocytes, which consist of collagen fibers embedded with the gel-like aggrecan.…”