Degenerative disc disease (DDD) is a condition associated with the degeneration of one or more of the discs in the spine. DDD can cause severe chronic pain in the low back which can radiate to the hips and legs. There can be severe inflammation and degeneration of the fibrocartilage.
Recent studies have focused on the use of adult stem cells for disorders such as degenerative disc disease. Mesenchymal stem cells (MSCs) are non-hematopoietic, multipotent progenitor cells, which can be isolated from various human adult tissues. The potential to form cells of multi-lineages has indicated the potential of these cells in cases of degenerative disc disease. In recent years, MSCs have been shown to possess broad range of regenerative capabilities, modulating disease progression repairing lesions so closely associated with degenerative disc disease [1, 2]. MSCs are being investigated as a regenerative biologic agent because of their ability to differentiate into multiple tissue types and to self-renew.
The paracrine activity of MSCs is thought to be one of the major means by which these cells mediate anti-inflammatory, anti-apoptotic, anti-fibrotic, angiogenic, mitogenic and wound healing properties. The complex interplay of the biological mediators secreted by MSCs has been shown to be important in regulating regeneration of damaged or diseased organs and tissues of the body. It has also been shown that the pre-curser to the MSC is the pericyte which are the cells present on the microvessels and capillaries throughout the body. These cells become “activated” when an injury is recognized and detach to become medicinal MSCs. An immune-modulatory effect is initiated where other cells are called to help with the healing process while other secreted molecules will establish a regenerative microenvironment by setting up a trophic field [3].
Recent studies have identified adipose tissue as a new source of mesenchymal stem cells. As lipoaspiration provides relatively simple access to this stem cell pool, and with the large numbers of cells present in adipose tissue, its future potential as a stem cell reservoir for degenerative disc disease is promising.
Stem cells derived from a patient’s own fat are referred to as adipose-derived stem cells [4]. Adipose-derived stem cells or ADSCs are multi-potential in that they have the ability to differentiate into a variety of different types of tissue including but not limited to bone, cartilage, muscle, and fat. These cells have also been shown to express a variety of different growth factors and signaling molecules (cytokines), which recruit other stem cells to facilitate repair and healing of the affected tissue. ADSCs are very angiogenic in nature and can promote the growth of new blood vessels. In addition, ADSCs might play a role in the local inflammatory process [5, 6].
A stromal vascular fraction (SVF) can easily be isolated from fat tissue in approximately 30–90 min in a clinic setting using a mini-lipoaspirate technique. The SVF contains a mixture of cells including ADSCs and growth factors and has been depleted of the adipocyte (fat cell) population. It has been shown that cells isolated from the SVF contain an abundance of CD34+ cells [7]. This marker is present on both pericytes and mesenchymal cells. Cells expressing CD34 are also known to reside in a periendothelial location and stabilize endothelial networks. SVF can be used in a point of care setting for a variety of indications and is currently being used in thousands of clinics world-wide with varying degrees of success reported. Adipose tissue is quickly becoming the preferred source for point of care treatments in clinic due to the high number of MSCs that can be obtained and the low number of leukocytes as compared to bone marrow [8]. In addition, adipose tissue has a significantly higher amount of pericytes which are the precursors to MSCs [9, 10].
Stem cells from adipose tissue offer a novel therapy for patients with degenerative disc disease. SVF injected directly into the disc may reduce inflammation and promote healing. SVF is an attractive therapeutic method given that the harvesting process is safe and the cells are readily available in usually large quantities. In Vitro studies have demonstrated that ADSCs are able to stimulate matrix synthesis and cell proliferation of degenerated nucleus pulpous cells. This may promote the restoration of damaged nucleus cells in a degenerated disc [11]. In a murine model of chronic disc degeneration, ADSC transplantation promoted new expression of proteoglycans and increased levels of aggrecan [12]. ADSCs were also studied in a rabbit model of degenerative disc disease. The ADSC injected discs exhibited elevated extracellular matrix and minimal ossification as compared to the control discs [13].
Platelet rich plasma is a mixture of growth factors and fibrin obtained from autologous peripheral blood. PRP has been utilized in a variety of musculoskeletal indications with evidence of anti-inflammatory and healing properties. One study demonstrated that intradiscal injections of PRP led to symptomatic clinical benefit in individuals with chronic discogenic lower back pain [14]. By combining PRP with SVF, there may be an increased number of growth factors anad proteins which could translate to improved patient outcomes.
Pettine, et al. have reported on the use of bone marrow concentrate to treat discogenic pain as an alternative to surgery. The cells were injected directly into the nucleus pulposus with no complications reported. There was a 71% reduction in VAS pain scales and ODI improvements through 2 years [15]. In another pilot study, patients with degenerative disc disease were injected into the nucleus pulpous area with culture expanded autologous bone marrow MSCs. Patients exhibited rapid improvement of pain and disability and elevated water content in the disc at the 12 month follow up [16]. We report the safety and preliminary efficacy results of intradiscal SVF and PRP administration in patients with degenerative disc disease.