Stem Cell Regenerative Medicine A New Hope in Orthopedics
Stem cell regenerative medicine is the fastest emerging branch of medicine - Leland Kaiser introduced the term "Regenerative Medicine" in 1992. He already predicted that a new branch of medicine will develop that attempt to change the course of chronic disease & in many cases it will regenerate the exhausted and failing organ systems. Since then, Scientists around the world are making efforts to develop reverse time therapy to regenerate damaged tissues & organs.
The presented review will concentrate on advancement of stem cell regenerative medicine (SCRM) towards orthopedics. Large bone defects & Non Union Cases present a huge therapeutic challenge to the surgeon & these complications put extra financial burden on health care system & society, it is the reason for significant morbidity.
SCRM is a combination of neoosteogenesis & neovascularization, by which we can restore the tissue deficit. This optimal approach includes the knowledge of biomaterial scaffold, cell biology technique, growth factor required for stem cell growth & optimum mechanical environment.
SCRM is a fast growing & promising method for a wide variety of Orthopedic diseases and traumatic injuries. In several countries, scientific research about SCRM is promoted by providing more & more funds that's the reason, because of which many quality publications are coming in to light & moreover we are expecting further advanced innovations in the field of SCRM. Human and animals are commonly affected by orthopedic injuries in bone, muscle, tendons, cartilage and so on. Though natural healing power of bone is enough for normal healing process, massive trauma, and aggressive bone tumours can hamper regeneration power of osteogenic stem cells.
Mesenchymal cells (MSCs) have got the ability to develop in to any sort of mesodermal tissue, so that they could be directed to form precursor cells to develop in to several tissues like tendon, ligament, bone, cartilage, muscle. Stem cell regeneration therapy can be used in several conditions. Neen reported that unselected stem cells used with hydroxyapatite (HA) scaffolds had homologous healing rates as autologous grafting & it also prevent donor site morbidity. Bone Marrow aspirates containing stem cells in a ratio of 1:10000 to 1:1,000,000 of nucleated cells have been successfully used to enhance the healing in non-Union cases.
Animal experiments have shown increased proteoglycan content and maintenance of Disc height with percutaneous stem cell injection. Clinical trials are running to explore these results in humans with positive interim results. Effect of MSCs is positive in case of animal studies via intrathecal and local administration; however clinical studies response is mixed. Tamaki reported that muscle derived MSCs involved in regeneration of a crushed peripheral nerve has been done successfully.
Mostly data is based on animal studies showing use of MSCs suitable scaffolds in cartilage healing. Only a few human case studies have been done and shows improved functional outcome after autologous MSCs implantation techniques. Adams reported that stem cells used to treat rat with Achilles' tendon tear treated with stem cell containing sutures have higher failure strength and better histological characteristics. Unselected MSCs were used for ultrasound guided injections in a case series for chronic patellar tendinopathy with good clinical outcomes. Horwitz reported that systemic infusion of allogenic MSCs in six children with osteogenesis imperfecti showed improvement in bone mass & bone growth acceleration. Though the studies showed promise, clear demonstration that the cells involved to the benefits seen in the recipient is still in paucity so these studies are still controversial regarding use of MSCs for osteogenesis imperfecti treatment. Plank showed in a study on pig that MSCs with scaffolds used in physeal defects differentiated in to chondrocytes to give rise to hyaline cartilage & prevents bony bridge formation. Currently there is no clinical study available to support this study.
Another animal study presented by Guan used MSCs modified to express certain surface which enabled them to migrate to the periosteum leading increased bone mass. These methods can be used in the treatment of generalised bone diseases such as osteoporosis. In sum, Table 1 Shows most of the studies are favour of SCRM, and in maximum number of studies showing positive results in osteonecrosis, osteoarthritis, spinal cord injury, fracture healing, patellar tendinopathy, cartilage defect, osteochondral defect, bone cyst, osteochondral talus defect, and non-Union cases. On the other hand in few studies SCRM results are comparable to conventional treatment and Buda study (2010) stem cell therapy shows No Significant improvement as compared autologous chondrocyte implantation. Above studies also prove the safety of Stem cell regenerative medicine.
The presented review and analysis obviously has its own limitations because we choose limited number of studies. Core weakness of this study is lack of powerful data and heterogeneity of data to reveal the outcome of SCRM in different orthopedic procedure, so we could not compare all outcomes together. Some unidentifiable and hidden factors might be the limitations of our study. Other important studies about SCRM may be missed because of language barrier.
From the above study, it is quite clear that we need more clinical trials to overcome the contradiction between success and failure of SCRM, so that SCRM can be used safely and effectively in orthopedics & other branches of medicine. Last but not the least, because maximum number of clinical trials and animal experimental studies demonstrated the effectiveness of SCRM that's why we strongly suggest that SCRM has got a great potential in Orthopedics.
Journal of Stem Cell Biology and Transplantation