intradiscal stem cell

OBJECTIVES: We aim to evaluate the benefits and harms of intervertebral disc therapies (IDTs) in people with non-specific chronic low back pain (NScLBP). METHODS: We conducted a systematic review and meta-analysis of randomized trials of IDTs versus placebo interventions, active comparators or usual care. EMBASE, MEDLINE, CENTRAL and CINHAL databases and conference abstracts were searched from inception to June 2020. Two independent investigators extracted data...

BACKGROUND: Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have emerged as a promising new therapeutic strategy for intervertebral disc degeneration (IVDD). However, the drawbacks of MSCs, including their invasive access, the donor age, and their limited proliferative capacity, hinder the quantity and quality of MSC-sEVs. Induced pluripotent stem cell-derived MSCs (iMSCs) provide an indefinite source of MSCs with well-defined phenotype and function. This study aimed to investigate the therapeutic effect of sEVs derived from iMSC (iMSC-sEVs) on IVDD and explore the underlying molecular mechanisms...

PURPOSE: With the aging population, it is clear that the demand for future chronic pain treatment modalities is at an all-time high. One of the newest treatment modalities that is gaining popularity with both practitioners and patients alike is that of regenerative medicine and the use of stem cells to treat chronic painful conditions. This article aims to distill the most recent, available data from both laboratory research and clinical trials to better illuminate the potentials for these therapies in the treatment of chronic pain...

Degenerative disc disease (DDD) is the leading cause of chronic back pain. It is a pathologic condition associated with aging and is believed to result from catabolic excess in the intervertebral discs' (IVD) extracellular matrix. Two new treatment options are intradiscal cellular transplantation and growth factor therapy. Recent investigations on the use of these therapies are discussed and compared with emerging evidence supporting novel cellular injections. At present, human and animal studies provide a compelling rationale for the use of cellular injections in the treatment of discogenic pain...

Intervertebral disc (IVD) degeneration can cause chronic lower back pain (LBP), leading to disability. Despite significant advances in the treatment of discogenic LBP, the limitations of current treatments have sparked interest in biological approaches, including growth factor and stem cell injection, as new treatment options for patients with chronic LBP due to IVD degeneration (IVDD). Gene therapy represents exciting new possibilities for IVDD treatment, but treatment is still in its infancy. Literature searches were conducted using PubMed and Google Scholar to provide an overview of the principles and current state of gene therapy for IVDD...

STUDY DESIGN: Post hoc comparison using single-site data from 4 multicenter randomized controlled trials. OBJECTIVES: Discogenic back pain is associated with significant morbidity and medical cost. Several terminated, unreported randomized controlled trials have studied the effect of intradiscal biologic injections. Here we report single-center outcomes from these trials to determine if there is clinical improvement associated with these intradiscal injections. METHODS: Post hoc comparison was performed using single-site data from 4 similar multi-center randomized controlled trials...

BACKGROUND: The purpose of our study was to examine the effect of controlled delivery of TGF-β3 , BMP-4, and TIMP-2 with a biocompatible biopolymer, chitosan, on an acutely injured intervertebral disc (IVD) in a rabbit model. METHODS: After conducting an in vitro analysis of the chondrogenic capacity of the biomolecule cocktail use (ie, TGF-β3 , BMP-4, and TIMP-2) and confirming stem cell viability in chitosan hydrogel, 15 New Zealand white rabbits underwent a lateral approach of the L1 to L4 IVDs...

BACKGROUND: There are an overwhelming number of patients suffering from low back pain (LBP) resulting from disc pathology. Although several strategies are being developed pre-clinically, simple strategies to treat the large number of patients currently affected is still needed. One option is to use concentrated bone marrow aspirate (cBMA), which may be effective due to its intrinsic stem cells and growth factors. METHODS: Thirty-three patients who received intradiscal injections of cBMA to relieve LBP were followed up based on Numeric Rating Scale (NRS), Oswestry Low Back Pain Disability Index (ODI), and Short Form-36 Health Survey (SF-36) scores...

Intervertebral disc (IVD), a moderately moving joint located between the vertebrae, has a limited capacity for self-repair, and treating injured intervertebral discs remains a major challenge. The development of innovative therapies to reverse IVD degeneration relies primarily on the discovery of key molecules that, occupying critical points of regulatory mechanisms, can be proposed as potential intradiscal injectable biological agents. This study aimed to elucidate the underlying mechanism of the reciprocal regulation of two genes differently involved in IVD homeostasis, the miR-221 microRNA and the TRPS1 transcription factor...

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Background: Forty percent of low back pain cases are due to intervertebral disc degeneration (IVDD), with mesenchymal stem cells (MSCs) a reported treatment. We utilized an ovine IVDD model and intradiscal heterologous MSCs to determine therapeutic efficacy at different stages of IVDD. Methodology: Three nonoperated control (NOC) sheep were used for MSC isolation. In 36 sheep, 6 × 20 mm annular lesions were made at three spinal levels using customized blades/scalpel handles, and IVDD was allowed to develop for 4 weeks in the Early (EA) and late Acute (LA) groups, or 12 weeks in the chronic (EST) group...

Intervertebral disc degeneration (IVDD) is a progressive condition marked by tissue destruction and inflammation. The therapeutic effector functions of mesenchymal stem cells (MSCs) makes them an attractive therapy for patients with IVDD. While several sources of MSCs exist, the optimal choice for use in the inflamed IVD remains a significant question. Adipose (AD)- and amnion (AM)-derived MSCs have several advantages compared with other sources, however, no study has directly compared the impact of IVDD inflammation on their effector functions...

Background: Cell replacement therapy is an attractive alternative for treating degenerated intervertebral discs (IVDs), which are related to the reduction of nucleus pulposus-like cells (NP-lCs) and the loss of the extracellular matrix. Induced pluripotent stem cells (iPSCs) which resemble embryonic stem cells are considered to be a potential resource for restoring NP-lCs and disc homeostasis. Here, we proposed an efficient two-step differentiation protocol of human iPSCs into NP-lCs and continuously tested their in vivo ability to regenerate IVDs...

BACKGROUND: Regenerative medicine is a medical subspecialty that seeks to recruit and enhance the body's own inherent healing armamentarium in the treatment of patient pathology. This therapy's intention is to assist in the repair, and to potentially replace or restore damaged tissue through the use of autologous or allogenic biologics. This field is rising like a Phoenix from the ashes of underperforming conventional therapy midst the hopes and high expectations of patients and medical personnel alike...

Low back pain is a major cause for disability and is closely linked to intervertebral disc degeneration. Mechanical and biological dysfunction of the nucleus pulposus in the disc has been found to initiate intradiscal degenerative processes. Replacing or enriching the diseased nucleus pulposus with an injectable, stem cell-laden biomaterial that mimics its material properties can provide a minimally invasive strategy for biological and structural repair of the tissue. In this study, injectable, in situ-gelling carboxymethylcellulose hydrogels were developed for nucleus pulposus tissue engineering using encapsulated human marrow-derived mesenchymal stromal cells (hMSCs)...

BACKGROUND: Adipose tissue-derived mesenchymal stem cells (AT-MSCs) offer potential as a therapeutic option for chronic discogenic low back pain (LBP) because of their immunomodulatory functions and capacity for cartilage differentiation. The goal of this study was to assess the safety and tolerability of a single intradiscal implantation of combined AT-MSCs and hyaluronic acid (HA) derivative in patients with chronic discogenic LBP. METHODS: We performed a single-arm phase I clinical trial with a 12-month follow-up and enrolled 10 eligible chronic LBP patients...

BACKGROUND: Stem cells from adipose tissue offer a novel therapy for patients with damaged tissue. Stromal vascular fraction (SVF) injected into patients may reduce inflammation, promote healing, and repair damaged/scarred tissue. SVF can be isolated from fat (adipose) tissue in an outpatient procedure. The SVF population includes mesenchymal stem cells (MSCs), pericytes, endothelial/progenitor cells, fibroblasts and growth factors where the adipocyte (fat cell) population has been removed...

BACKGROUND: Degenerative disc disease (DDD) is a common cause of lower back pain with radicular symptoms and has a significant socioeconomic impact given the associated disability. Limited effective conservative therapeutic options result in many turning to surgical alternatives for management, which vary in the rate of success and also carry an increased risk of morbidity and mortality associated with the procedures. Several animal based studies and a few human pilot studies have demonstrated safety and suggest efficacy in the treatment of DDD with mesenchymal stem cells (MSCs)...

Although mesenchymal stem cells (MSCs) transplantation into the IVD (intervertebral disc) may be beneficial in inhibiting apoptosis of nucleus pulposus cells (NPCs) and alleviating IVD degeneration, the underlying mechanism of this therapeutic process has not been fully explained. The purpose of this study was to explore the protective effect of MSC-derived exosomes (MSC-exosomes) on NPC apoptosis and IVD degeneration and investigate the regulatory effect of miRNAs in MSC-exosomes and associated mechanisms for NPC apoptosis...

Degeneration of the intervertebral discs is a progressive cascade of cellular, compositional and structural changes that is frequently associated with low back pain. As the first signs of disc degeneration typically arise in the disc's central nucleus pulposus (NP), augmentation of the NP via hydrogel injection represents a promising strategy to treat early to mid-stage degeneration. The purpose of this study was to establish the translational feasibility of a triple interpenetrating network hydrogel composed of dextran, chitosan, and teleostean (DCT) for augmentation of the degenerative NP in a preclinical goat model...