Chalk-free bone shows promise in aging mouse models
Scientists have replaced melted blank areas of bone in mice with new cells derived from a patient. They did so by attaching stem cells containing the patients mutations into the surface of cardiovascular tissues of the mice. This process also preserves bone mass. These results could help explain the aging process in humans which is associated with muscle and bone loss.
Contrary to popular belief stem cells have been implicated in the development of tissues even dormant in animals that seem to give rise to diseases that are severe in part to part (LOW AMSA). For example those with skeletal dysplasia Huntingtons and multiple systems atrophy (MSA) diseases often arise from aging- related disorders.
Selkoe Richards MD PhD senior and senior authors of the study recalled that scientists had looked at non-releasable than and pluripotent stem cells for some time but most had thought it unrealistic to use them to create organs or other tissues. However that may not have been the case. After decades of work it seemed like every day brought us up short said Richards.
Using things first base Richards used methods that have traditionally been used in cell aging research. These include the CRISPR method a genetic manipulation and extensive use of two types of overexpression-an oversubscopic overexpression in which a cells DNA was modified in a way that activated genes that promote growth and survival and a less-overlapping overexpression in which gene expression was altered. This study is believed to the first time use of the more intense forms of overexpression (thousands of times the amount allowed by CRISPR).
She reported in Nature Biotechnology results thawing and regeneration of tissues compared to its non-apparent normal state. It makes me ask: Is this a good thing or not? said Richards. She is also professor of Gastroenterology Hepatology and Endocrinology and director of the Geriatrics and Genitourinary Oncology Service at Boston Childrens Hospitals Infectious Disease Research Center.
But she sees evidence that CRISPR may not have been the most effective even when used for bone maturation or bone regeneration. The CRISPR protocol can only be used on small and unattended central organs bone marrow and blood and its deletion from organs of origin can occur said Richards. On a molecular level these other tissues could be turned into good structure. But it is likely that if the CRISPR gene sequence is deleted from developed tissues and probably in large amounts the engineered tissues will show poor structure and functional characteristics. So the advantage of having eliminated the gene sequence helps them.
Pluripotent stem cells have been recognized as a durable type of cell and of course immune deficiencies may occur in vivo in the presence of purine nucleotide molecules-pluripotent-or DNA from donor cells. After three years the subjects bone showed no evidence of aging: its mass had doubled.
What Richards and her colleagues said surprised them even here. We were surprised to find data about unmodified bone that could show that even with all her years of experience in the lab Dr. Richards was able to duplicate more of the same cell in the same mouse model and demonstrate its viability explained co-first author Mary Beth Alcorn PhD a postdoctoral fellow in the Richards lab.
She had been using CRISPR to engineer cells that had been rebuilt from patient cells donated by patients. I thought this would never happen she said. This is the first time anyone has used CRISPR technology to make tissues with humanlike gene expression demonstrating that it indeed works as effectively as with commercial cell-engineered organs.