As my nerdy self did the hourly rounds of scrolling each news source app on my phone on November 16th, I came across the headline, "Leprosy: Ancient disease able to regenerate organs" on BBC. Let me tell you, there is hard evidence to back this wild title.
Promoting the growth of organs is the most effective treatment for disease, injury, and aging in adults. Unfortunately, no such treatment exists (Hess et al., 2022). The newest treatments for organ failure and aging target cells at genetic levels to promote regeneration.
In 2013, a group of scientists from the University of Ediburgh discovered that Mycobacterium leprae (ML), the bacteria responsible for leprosy, hijacked Schwann cells and caused them to be reprogrammed into a progenitor cell/stem cell state by demethylation of SOX10 (Masake et al., 2013). This was some of the earliest research exploring the effect of ML on organ regeneration.
(Masaki et al., 2013)
Almost ten years later, another group of scientists primarily from the University of Edinburgh published findings that ML-infected nine-banded armadillos had larger livers without loosing liver function or shape or causing damage (Hess et al., 2022).
Why armadillos? Nine-banded armadillos are the only mammals to produce four genetically identical litters and are natural hosts of ML (Hess et al., 2022). Why the liver? The liver happens to be the most exemplar organ for studying growth, since it can reach its prior mass after tissue loss. Because of its highly restorative capacity, the liver is subject to malignancy due to the high turnover rate of cells (Hess et al., 2022). ML-infection of the nine-banded armadillo and subsequent study of the liver resulted in the perfect in vivo (Latin for "within a living organism") experiment to determine the actual regenerative outcome of ML.
(Hess et al., 2022)
(Hess et al., 2022)
Data collected by the scientists supported their hypothesis that ML infection caused in vivo liver development of progenitor cells. Fetal liver progenitor genes, which are expressed in armadillos and humans alike, were expressed in significantly higher amounts in ML-infected livers. FOXA transcription factors, responsible for embryonic hepatocyte specification, were upregulated. LGR4 and LGR5, promoters controlling growth factors, were also upregulated. On the other hand, genes associated with aging, such as IGFBP5/1/2, were downregulated. There were no differences between oncogene and tumor-suppressor gene expression between infected and non-infected livers (Hess et al., 2022).
The infected livers maintained proper function. Metabolic markers, such as bile acid-CoA:amino acid N-acyltransferase (BAAT for short and responsible for making bile) and albumin, were present in normal amounts. Since ML requires fats to survive, genes responsible for lipid metabolism were upregulated, but the fat did not accumulate within the liver, which proves that the ML was using the fats to survive. This did not cause any problems (Hess et al., 2022).
The livers from all ML-infected armadillos were enlarged and by similar proportions, and tumors were not found. There was no evidence of edema nor liver disease, and capillaries remained the same diameter. There were more binucleated hepatocytes, as well as more non-hepatocyte cells (including immune and endothelial cells) in infected livers, but this was not statistically significant, which means that these cells were not responsible for the increased liver mass. Livers infected with ML increased lobule number in vivo, without injury, aging, fibrosis, or tumor formation (Hess et al., 2022).
So, if 95 percent of humans immediately clear ML upon natural infection (Hess et al., 2022), and liver disease is the 12th leading cause of death in the U.S. (Asrani et al., 2013), perhaps infecting people with Mycobacterium leprae will be part of patient treatment plans in the near future.
References
Asrani, SK., Larson, JJ., Yawn, B., Therneau, TM., Ray Kim, W. (2013, August). Underestimation of Liver-Related Mortality in the United States. American Gastroenterological Association. https://doi.org/10.1053/j.gastro.2013.04.005
Hess, S., Kendall, TJ., Pena, M., Yamane, K., Soong, D., Adams, L., Truman, R., & Rambukkana, A. (2022, November 15). In vivo partial reprogramming by bacteria promotes adult liver organ growth without fibrosis and tumorigenesis. Cell Reports Medicine. https://doi.org/10.1016/j.xcrm.2022.100820
Masaki, T., Qu, J., Cholewa-Waclaw, J., Burr, K., Raaum, R., & Rambukkana, A. (2013, January 17). Reprogramming Adult Schwann Cells to Stem Cell-lik Cells by Leprosy Bacilli Promotes Dissemination of Infection. Cell Reports Medicine. https://doi.org/10.1016/j.cell.2012.12.014
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