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Frank J. Garcia M.D. Regenerative Medicine Written by: Frank J. Garcia M.D.
Issue: July 2010 | NSIDE Medical
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A new frontier in orthopedic use of stem cells Regenerative Medicine

The use of stem cells in orthopedics has seen significant advances in the past few years and there seems to be exponential breakthroughs in current research information. This review article contains current information on the use or potential use of stem cells in orthopedics.

Stem cells have two distinct properties. First, they can make identical copies of themselves for an indefinite period of time; and second, they give rise to mature cells that have characteristic morphology and function.

Stem cells are derived from three main sources: embryos, the umbilical cord and adult tissue. Embryonic stem cells are defined by their origin, which is from one of the earliest stages of development, the blastocyst. These cells can self-replicate and are pluripotential.

Umbilical cord stem cells are harvested from cord blood. It is rich in stem cells. Characteristics of these cells are identical to adult stem cells but their concentration has far more potential in harvesting a critical number of stem cells versus adult tissue.

Adult stem cell is an undifferentiated cell that is found in different tissue such as bone marrow and adipose tissue. These cells can renew and become specialized to yield all the specific cell types of tissue from which it originated. They are not pluripotential. Adult stem cells are rare and their primary function is to maintain homeostasis.

In the 1970s the embryonic chick limb bud mesenchymal cell culture system provided data on differentiation of cartilage, bone and muscle. In the 1980s this cell system was used for the purification of inductive factors in bone. In the 1990s tissue engineering was accomplished where mesenchymal stem cells (MSCs) were used with specific delivery vehicles to repair cartilage, bone, tendon, marrow stroma, muscle and other tissues.

The 21st century has seen advances that allow introduction of informational proteins to the outer surface of cells. This “cell painting” can serve as targeting addresses to specifically dock MSCs or other reparative cells. Stem cells do not necessarily have to differentiate into new tissue to mediate therapeutic effects, but can do this in many cases simply by producing growth factors that activate resident stem cells.

Orthopedic applications: Spinal Cord Regeneration
Injury to neural tissue results in permanent deficit as neurons do not have the ability to repair or regenerate. In animal experiments cultured spinal cord stem cells have been implanted in rat models of spinal cord injuries and they were shown to differentiate and improve motor function. Human experiments involving paraplegic patients are still in the distant future in the United States. Other countries are reporting results on human trials that concur with the improvement seen with animal experiments.

Bone defects and non-unions
The ideal modality for treatment of these problems is autologous bone grafting, however, the amount of graft remains limited and the harvest site morbidity limits its use. Clinical trials using adult stroma stem cells to fill in critical bone defects have shown efficacy in both direct injection at the lesion and where ex vivo expansion and implantation methods were used.

Cartilage Repair
Articular cartilage has limited repair and regeneration potential. All treatments to date produce hyaline like cartilage that is inferior for the functional demands of most joints. Biologic solutions for cartilage injuries would be preferable over joint arthroplasty. Success has been shown with periostial derived stem cells in the repair of osteochondral defects.

Mesenchymal stem cells can differentiate along both osteogenic and chondrogenic linage and are seen as ideal for the possibility for cartilage regeneration. Multiple requirements, including growth factors, signaling molecules, and physical influences need to be met. Adult mesenchymal stem-cell-based tissue engineering is a promising technology for the development of a transplantable cartilage replacement to improve joint function.

ACL and Meniscus Reconstruction;
In a recent animal study, ACL reconstructions were coated with stem cells, and it was shown that the incorporation at the chondral zone was more like normal ACL insertions and biomechanically proved to be stronger. Similar regeneration was found in meniscal defects in the avascular zone. Stem cells seem to show promise as a strategy for the treatment of both ACL and meniscus injuries.

Vertebral Disc Degeneration
Degenerative disc disease (DDD) is a common disease, which affects millions of people. In a recent paper the use of bone marrow stem cell injection into degenerating discs was assessed. After treatment with mesenchymal stem cells, regeneration of the pulposus was observed based on increased disc space, upregulation of genes encoding for proteoglycans as well as other extracellular matrix components.

It was demonstrated that the mesenchymal stem cells differentiated into chondrocyte-like cells, but perhaps more interestingly, the progenitor cells of the nucleus pulpous, called notochordal cells, entered cell cycle and generated extracellualar matrix, thus contributing to the repair process.

There remains much controversy in the use of stem cell research including costs, political, ethical and public opinion. On the clinical side, issues of adequate concentration from adult stem cell harvest, modulating cell function, risk of forming unwanted tissue and risk of cancer formation require further evaluation and long-term follow up.

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