Potential of Mesenchymal Stem Cells to Treat Low Back Pain in Animal Model

Abstract

Degenerative disc disease (DDD) involves the breakdown of intervertebral discs (IVDs), which can cause chronic neck and lower back pain. The IVD consists of a gel-like nucleus pulposus (NP) at its center, encased by a tough outer layer called the annulus fibrosus (AF). Current treatments mainly aim to relieve symptoms rather than repair the discs structure and function. Recently, research has begun to focus on cell therapy for DDD, particularly using adult mesenchymal stem cells (MSCs) We have isolated mesenchymal stem cells (MSCs) from perinatal tissues, specifically the umbilical cord, using a xenofree medium developed in our lab. We call these cells primitive (p) MSCs because they not only express typical MSC markers, such as CD29, CD44, CD73, CD90, and CD105—but also several self-renewal markers, including CD49f, OCT4, NANOG, SOX2, and KLF4. pMSCs expanded in xenofree medium are suitable for therapeutic applications. We have successfully differentiated pMSCs into nucleus pulposus-like cells (NPCs) that express characteristic markers, including SOX9, ACAN, COL2, TGFβ1, TGFβ3, VCAN, and GDF10. Additionally, we have developed three-dimensional (3-D) scaffolds that mimic the native environment of the IVD. We hypothesize that pMSCderived NPCs can regenerate the nucleus pulposus of the IVD. The aims of this study are as follows: 1. To isolate mesenchymal stem cells (MSCs) using a xenofree medium. 2. To differentiate MSCs into nucleus pulposus-like cells (NPCs). 3. To develop three-dimensional (3-D) scaffolds that mimic the in vivo microenvironment of the intervertebral disc (IVD). 4. To investigate the effectiveness of combining cells and scaffolds transplanted in a rat model of lower back pain (LBP). These objectives will be achieved using behavioral assays, MRI analysis, and various biochemical, immunological, and molecular biology techniques. Overall, this research establishes a foundation for clinical studies aimed at regenerating the IVD and alleviating pain and suffering in patients with DDD.