Angiocrine growth factors

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Angiocrine growth factors are molecules found in blood vessels' endothelial cells that can stimulate organ-specific repair activities in damaged or diseased organs. Endothelial cells possess tissue-specific genes that code for unique growth factors, adhesion molecules and factors regulating metabolism. [1] [2]

The discovery emerged after the entirety of active genes in endothelial cells was decoded, resulting in an atlas of organ-specific blood vessel cells. The atlas documented hundreds of already-known genes that had never been associated with these cells. Organs dictate the structure and function of their own blood vessels, including the repair molecules they secrete. Each organ produces blood vessels with unique shape and function that comply that organ's metabolic demands. [1] [3]

Organ repair

When an organ is injured, its blood vessels may not be able to repair the damage because they may themselves be damaged or inflamed. An infusion of engineered endothelial cells may be able to engraft into injured tissue and acquire the capacity to repair the organ. [1]

Endothelial cells generated from mouse embryonic stem cells were functional, transplantable and responsive to microenvironmental signals. Such cells can be transplanted into different tissues, become educated by the tissue and acquire the characteristic phenotype of that organ type's endothelials. Such cells were transplanted into the liver and kidney of mice and found became indistinguishable from existing endothelial cells. [1]

In a clinical setting the cells must be immunocompatible with the recipient patient. They could be derived from the patient's embryonic pluripotent stem cells as well as by somatic cell nuclear transfer (SCNT). In SCNT the nucleus is introduced into a human egg producing embryonic stem cells that are a genetic match of the patient. Another approach takes cells discarded after a diagnostic prenatal amniocentesis. [1]

Additional preclinical investigation is required before investigation with humans. [1]

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Angiogenesis blood vessel formation when new vessels emerge from existing vessels

Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting. Vasculogenesis is the embryonic formation of endothelial cells from mesoderm cell precursors, and from neovascularization, although discussions are not always precise. The first vessels in the developing embryo form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during development and in disease.

Somatic cell nuclear transfer

In genetics and developmental biology, somatic cell nuclear transfer (SCNT) is a laboratory strategy for creating a viable embryo from a body cell and an egg cell. The technique consists of taking an enucleated oocyte and implanting a donor nucleus from a somatic (body) cell. It is used in both therapeutic and reproductive cloning. Dolly the Sheep became famous for being the first successful case of the reproductive cloning of a mammal. In January 2018, a team of scientists in Shanghai announced the successful cloning of two female crab-eating macaques from fetal nuclei. "Therapeutic cloning" refers to the potential use of SCNT in regenerative medicine; this approach has been championed as an answer to the many issues concerning embryonic stem cells (ESC) and the destruction of viable embryos for medical use, though questions remain on how homologous the two cell types truly are.

Transplant rejection

Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after transplant.

Endothelium Inner lining of blood vessels

Endothelium refers to cells that line the interior surface of blood vessels and lymphatic vessels, forming an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. It is a thin layer of simple, or single-layered, squamous cells called endothelial cells. Endothelial cells in direct contact with blood are called vascular endothelial cells, whereas those in direct contact with lymph are known as lymphatic endothelial cells.

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Endothelial stem cell

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Ischemia-reperfusion (IR) tissue injury is the resultant pathology from a combination of factors, including tissue hypoxia, followed by tissue damage associated with re-oxygenation. IR injury contributes to disease and mortality in a variety of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease and sleep apnea. Whether resulting from traumatic vessel disruption, tourniquet application, or shock, the extremity is exposed to an enormous flux in vascular perfusion during a critical period of tissue repair and regeneration. The contribution of this ischemia and subsequent reperfusion on post-traumatic musculoskeletal tissues is unknown; however, it is likely that similar to cardiac and kidney tissue, IR significantly contributes to tissue fibrosis.

Craniofacial regeneration refers to the biological process by which the skull and face regrow to heal an injury. This page covers birth defects and injuries related to the craniofacial region, the mechanisms behind the regeneration, the medical application of these processes, and the scientific research conducted on this specific regeneration. This regeneration is not to be confused with tooth regeneration. Craniofacial regrowth is broadly related to the mechanisms of general bone healing.

References

  1. 1 2 3 4 5 6 "Blood vessel cells can repair, regenerate organs, scientists say". Medicalxpress.com. Retrieved 2013-10-11.
  2. Nolan, D. J.; Ginsberg, M.; Israely, E.; Palikuqi, B.; Poulos, M. G.; James, D.; Ding, B. S.; Schachterle, W.; Liu, Y.; Rosenwaks, Z.; Butler, J. M.; Xiang, J.; Rafii, A.; Shido, K.; Rabbany, S. Y.; Elemento, O.; Rafii, S. (2013). "Molecular Signatures of Tissue-Specific Microvascular Endothelial Cell Heterogeneity in Organ Maintenance and Regeneration". Developmental Cell. 26 (2): 204–219. doi:10.1016/j.devcel.2013.06.017. PMC   3873200 . PMID   23871589.
  3. Israely, E.; Ginsberg, M.; Nolan, D.; Ding, B. S.; James, D.; Elemento, O.; Rafii, S.; Rabbany, S. Y. (2013). "Akt suppression of TGFβ signaling contributes to the maintenance of vascular identity in embryonic stem cell-derived endothelial cells". Stem Cells. 32: 177–190. doi:10.1002/stem.1521. PMC   4886558 . PMID   23963623.