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One of the major achievements in the development in modern medicine is the discovery of stem cells. Stem cells are attracting attention as a key element in future medicine, satisfying the desire to live a healthier life with the possibility that they can regenerate tissue damaged or degenerated by disease or aging. Development of cell therapy and regenerative medicine using stem cells is expanding the medical industry and businesses as well as increasing the understanding of the nature of the cell itself. Stem cell medicine brings a new paradigm to modern medicine which has relied heavily on medicine or surgery.

Definitions of stem cells

Stem cells are defined as undifferentiated cells that have the ability to replicate and differentiate themselves into various tissues cells. Stem cells play an important role in forming organs at the stage of embryonic development and restoring organs and renewing tissue functions in fully developed adults as well. Stem cells generate their daughter cells through symmetrical or asymmetrical cell division. Symmetrical divisions are defined as the generation of undifferentiated daughter cells like the parent cell, and unsymmetrical divisions are defined as the generation of differentiated daughter cells.

Stem cells that are often encountered in clinical or preclinical stages are largely classified into embryonic, adult, and induced pluripotent stem cells (iPSCs). Embryonic stem cells can be obtained from the inner cell mass of blastocysts, one of the embryonic stages.

Adult stem cells are present in all tissues or organs of the adult body. Even though they are small in number, these cells help repair and renew tissues or organs when the tissues are damaged or degraded.

Adult stem cells can be categorized into placenta and umbilical cord stem cells, hematopoietic stem cells, bone marrow-derived mesenchymal stem cells (MSCs), and adipose-derived MSCs (AMSCs), according to their origin.

MSCs are known to be suitable for allografts due to not having major   molecule class 2 and having only a small amount of class 1. This means that MSCs are not immunologically privileged, and could be considered merely ‘immune evasive’.

How to obtain MSCs

Stem cells can be harvested from liposuction or excised adipose tissue. Tissue samples obtained from liposuction are digested in a buffer solution containing collagenase with intermittent shaking. The digested solution is centrifuged and separated into the extracellular matrix with the oil in the upper layer and the cell layer precipitated at the bottom. The precipitated layer is called the stromal vascular fraction (SVF), which contains adipose stem cells.

Stem cells in pain medicine

Recently, stem cells transplantation has been frequently applied to the treatment of pain as an alternative or promising approach for the treatment of severe osteoarthritis, neuropathic pain and intractable musculoskeletal pain which does not respond to conventional medicine. Stem
cell-based therapies have been realized to be a potential treatment option for articular cartilage repair in patients with knee osteoarthritis , neuropathic pain, and intervertebral disc disease.

Osteoarthritis

Degeneration and inflammation of the cartilage that covers the joint surface is the main cause of pain in osteoarthritis. The cartilage of the articular surface reduces the friction of the joint motion and acts as a cushion against weight loading. While chondrocytes occupy only 1% to 5% of cartilage volume, they produce collagen, proteoglycans, and hyaluronan, which are components of the extracellular matrix, and maintain cartilage structure and physical properties. However, as the cartilage has no blood vessels and nerves, cartilage regeneration is difficult once the cartilage has been damaged or undergone degenerative changes.

Repaired tissues treated with MSCs appeared to have better cell arrangement, subchondral bone remodeling, and integration with surrounding cartilage than did repaired tissues generated by chondrocyte implantation.

The therapeutic modalities applied for osteoarthritis include surgical intervention or arthroscopy, tissue engineering, and intra-articular injection of cultured stem cells. These modalities would be applied individually or in combination. Microfractures are made artificially under
arthroscopy by awls which are used to make holes through the subchondral bone plate to become focal full-thickness cartilage defects. This procedure is intended to allow the migration of stem cells in the bone marrow to reach the cartilage defect site. In this case, the cartilage produced by
this procedure tends to become less durable fibrous cartilage in comparison to the innate hyaline cartilage.

Intervertebral disc disease

The expression of TNF-α and IL-8 in the nucleus pulposus of degenerated discs was much higher than that of herniated discs. That would be a reason why the level of pain is more severe in patients with a degenerated disc [102]. When patients with degenerative disc disease were treated
with autologous expanded bone marrow MSCs injected into the nucleus pulposus, the pain and disability were improved, and were comparable to spinal fusion surgery, although disc height was not recovered.

Patients with fractures of the trabecular bone and intervertebral discs with a complete radial fissure were excluded because the non-integrity of the annulus may allow the injected stem cells to escape. Patients with low back pain due to initial intervertebral disc degeneration and low-stage radiological degeneration were eligible for the stem cell infiltration.