Novel Device to Achieve Intervertebral Disc Regeneration Using Human Stem Cell Generated Nucleus Pulposus Cells
Stem Cell Disc Regeneration
(CURRENTLY NOT IN CLINICAL USE)
Mick J. Perez-Cruet MD MS; John Pepper; Naimisha Reddy Beeravolu MS; Jared Brougham MD; Christina Marie McKee MS; Rasul Chaudhry PhD
Department of Neurosurgery, OUWB School of Medicine, Royal Oak, MI; Department of Biological Science, Oakland
Biologic disc regeneration is arguably the ‘holy grail’ of the spine industry. If we can develop a way to regenerate the intervertebral disc after injury or chronic aging, many patients suffering from chronic spine disorder would benefit. The goal of our research is to restore the inner core of the intervertebral disc using a combination of nucleus pulposus stem cells in combination with our proprietary disc distraction system called Annulo.
The nucleus pulposus consists mainly of water and collagen fibers providing an elastic-like structure that separates the vertebrae in our spine and withstands the many stresses placed upon it in daily life. Sadly, over time this inner core degenerates and can lead to chronic painful spinal conditions.
We are working on the restorative potential of this inner core through our Annulo Project. Our group has been researching the viability of nucleus pulposus regeneration through the use of Umbilical Cord Blood (UCB) stem cells. Initially recognized for its therapeutic potential over 30 years ago, UCB stem cells are an other-wise discarded medical waste after birth that can be used in many ways. They were used to treat a child with Fanconi’s anemia in France in 1980. Today, UCB is used for the treatment of over 80 life-threatening diseases, including a wide range of cancers, genetic diseases, immune system deficiencies and blood disorders.
We encourage you to review the information below concerning our research into this dynamic field of study.
Intervertebral disc (IVD) degeneration is characterized by the loss of nucleus pulposus (NP) leading to disc space collapse which is a common cause of low back pain (Fig. 1). Currently, degenerative disc disease (DDD) has no biological cure and human stem cell therapy is increasingly being considered for its treatment. However, stem cells alone may not be adequate to provide bio-mechanical disc height restoration. Disc restorative technology is being investigated that might restore the bio-mechanical function of the degenerated disc via a process of gradual tissue growth generated distraction (TGGD). Once disc height is restored the injection of nucleus pulposus cells (NPCs) can restore the biological function of the degenerated disc.
In this study, we investigated the feasibility of human umbilical cord mesenchymal stem cells (UC-MSCs) differentiated into NPCs invitro in an in-vivo rabbit model of DDD (Fig. 2). Histological, biochemical and gene expression analysis was preformed to determine the
optimal cell for NP regeneration (Fig.3). Further finite element analysis was preformed of a mechanical technology called Annulo (MI4Spine LLC, Bloomfield, MI) used to achieve disc height restoration.
Transplanted NPCs survived, integrated and displayed homing into nucleus pulposus (NP) of the rabbit degenerated disc with a significant improvement in the nucleus pulposus histology, cellularity, extracellular matrix proteins, water, and glycosaminoglycan contents (Figs. 4-5). In addition, the IVDs receiving NPCs had higher expression of nucleus pulposus specific human markers SOX9, ACAN, COL2, FOXF1, and KRT19. Finite element analysis of Annulo device revealed the optimal bio-mechanical forces needed to gradually restore disc height like Ilizarov (Figs. 6-10).
NPCs were efficient in regenerating the degenerated intervertebral disc and provide basis and impetus for clinical studies to treat DDD. A combination of TGGD technology can restore disc height first followed by injection of NPCs to restore the nucleus pulposus and may result in a viable biological treatment for patients suffering from DDD.