Human and Veterinary Regenerative Medicine

Written by: Sonakshi Mishra

Regenerative Medicine has become the newfound holy grail for the treatment of many previously intractable diseases whose recalcitrant cases had previously freighted the hearts of multiple medical professionals. Essentially, regenerative medicine is based on the idea of stem cell therapy, wherein stem cells[1] obtained from either the umbilical cord or the embryo can be programmed to differentiate into a required cell type for the regrowth, repair, or even replacement of damaged cells, organs or tissues. Its use has been coupled with tissue engineering and the production of artificial organs. Though the idea in itself dates back to the 1930s with the research and development of the first artificial perfusion pump by American aviator Charles Lindbergh and the French surgeon and biologist Alexis Carrell which incepted a cornerstone for the development of the artificial heart, the latest researches have opened up new frontiers for both human and veterinary medicine, transmogrifying the unimaginable feats in the field of medicine to occurrences currently deemed feasible under conducive work conditions. The newly emerging techniques of regenerative medicine involve extensive use of the bone-marrow-derived Mesenchymal stem cells (MSCs), a concept delved deep into and examined thoroughly, proving its efficacy in the treatment of various bones, cartilage, nervous, muscle, cardiovascular, blood, gastrointestinal diseases. Alongside these are the widely used biosynthetic materials or implantable scaffolds, which serve as the extracellular matrix, rendering functional and structural support and facilitating various factors including gene expression, proliferation, migration, differentiation, and more.

June 2021 has witnessed some applaudable discoveries in the field of human regenerative medicine ranging from newfound biomarkers to new promising sources of ex vivo manufacture of red blood cells, to engineering fully matured biomimetic cardiac tissues. Extensive studies carried out on the CD164 gene[2] in humans points towards its potential of becoming an excellent stem cell marker for hHPSC[3] and hSSC[4] isolation. Included in the research was the examination of glycosidase sensitivities of cell surface hCD164 sialomucin which revealed that the gene in itself contains Sialic acid (Sialic Acid can effectively promote the development and functional repair of nerve cells, epithelial cells, and immune cells)[5], and of the various glycans present in this gene, the O-glycan of this gene had a higher degree of sialylation. It is noteworthy, that aberrant sialylation is deemed an indicator of cancers as well as atypical immune systems, while sialylation in itself is associated with anti-inflammatory properties, opening frontiers for the use of stem cell therapies for numerous other purposes.[6] Additionally, in vitro studies carried out on the hCD164 Monoclonal antibodies communicates its roles linked with hematopoiesis, and in the proliferation, differentiation of other proteins and genes such as the CD34+ or the CD133++hHPSC.

The remarkable list of discoveries does not stop there. This month has also fished out another promising source of ex-vivo manufacture of red blood cells- immortalized erythroid cell lines and has contended Histone Deacetylase inhibitors (HDACi) as effective inducers of enucleation to boost the process involved in the ex-vivo manufacturing. Though, this is not bereft of its disadvantages that include weakening of the cell membrane, additional treatments to reinstate the levels of cell membrane protein- SPTA1 seems to rescue the technique from this setback. Further research will possibly involve more discoveries that will license the realization of the HDACi treatment to aid the ex-vivo manufacturing of red blood cells, allowing for the rescue of any blood shortage during any donor-dependent therapies or transfusions. The icing on the cake, though, has got to be the applaudable progress made in the laborious realm of cardiac tissue engineering. With the limited regenerative capacity of the adult human heart impeding smooth treatment of various cardiac conditions inclusive of damage caused to cardiac tissues etc., new techniques employed for the application of stem-cell-derived cardiomyocytes (CMs) apt for repair or replacement of damaged hearts, undoubtedly save a lot of our bacon. hPSC-CMs can develop adult-like features with training based on functional stimuli, cues to guide their structural organization, relevant biochemical factors, and by manipulating the genetic program.

Likewise, regenerative medicine has blessed the field of veterinary medicine as well, providing for an alternative to the majorly resorted surgical techniques that were previously rife when dealing with veterinarian conditions were in concern. These range from the new technological developments for assisted reproduction via spermatogonial cells which may be instrumental in the conservation of some endangered species today, to MSC[7] therapy for diseases such as the CCLD[8] and the nascent idea of PRP[9] treatment. Common conditions in dogs and cats include the CCLD, soft-tissue injuries, and degenerative disc diseases which stem from microtraumas caused to certain tendons and ligaments, which may cause cases of instability (especially during CCLD) and the progressive culmination of musculoskeletal problems into osteoarthritis in them. This inflicts approximately 40-60% of dogs. In due course, however, it may be possible to bid these problems adieu due to the application of MSC therapies which could ameliorate cell engraftment of the Cranial Cruciate ligament (one of the most crucial stabilizers in animals), while their intra-articular injection could even benefit their anterior crucial ligament. Better still, these MSCs are devoid of any ethical objections, making this technique a tempting one to be adopted in the field of veterinary regenerative medicine. New understandings of the PRP treatments also seem to indicate potential benefits for veterinary conditions. A study that examined 36 dogs using the BMAC[10]-PRP and ADPC[11]-PRP showed that PRP could also be a very useful therapy for conditions requiring regenerative restoration.

[1] Undifferentiated cells can differentiate into any type of cell and reproduce rapidly to produce copious quantities of it.

[2] More info on gene CD164: https://www.genecards.org/cgi-bin/carddisp.pl?gene=CD164

[3] Human Hematopoietic stem/progenitor cells

[4] Human skeletal stem cells

[5] More info on Sialic acid: https://vw-ingredients.com/sialic-acid-benefits

[6] Sialylation: https://www.sciencedirect.com/topics/medicine-and-dentistry/sialylation

[7] Mesenchymal stem cell

[8] Cranial Cruciate Ligament disease

[9] Platelet-rich plasma

[10] Bone marrow aspirate concentrate

[11] Adipose-derived progenitor cell

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