Renewing hope: Can stem cell-induced regeneration help reverse lung damage caused by Covid-19? | Photo Credit: anusorn nakdee
The bone marrow has till now been the single most common source of stem cells. However, other sources such as the umbilical cord or adipose tissue are being tapped too. Dr Geetanjali Tomar, scientist at Savitribai Phule Pune University, has been interested in the use of gingival cells (cells from oral gum tissue) in regenerative, or stem cell therapy since her PhD student days. In 2010, she co-authored a paper that, for the first time, highlighted the possibility of using gingival stem cells.
Her most recent paper appeared this year in June in Science Advances, the journal published by the American Association for Advancement of Science, in which she and her co-authors show that, irrespective of the age of the donor, stem cells from gingival tissue help regenerate neuronal cells [or nerve cells]. This finding, she says, could eventually help in the treatment of nerve-related disorders such as Parkinson’s and Alzheimer’s.
Why gingiva? Dr Tomar says, “It is very difficult to extract cells from the bone marrow. These would come from the knee cap of a donor who may not be healthy and is likely afflicted with arthritis or some such condition related to the bone.”
Plus, the recovery time after extraction of bone marrow tissue is more compared with that for gingival tissue.
“Extracting bone tissue is a highly invasive procedure. Gingiva offers no such complication. Anyone can donate gingival tissue and the healing time is about 7-10 days.”
Dr Tomar and her research team collaborated with Deenanath Mangeshkar Hospital and Research Centre in Pune to collect gum tissue from otherwise healthy patients undergoing root canal treatment, teeth extraction or crown implants. In lab conditions, the team discovered that the growth of the stem cell culture was uniform, irrespective of the donor’s age. Samples from even an 80-year-old showed normal growth. Typically, with age, stem cells tend to develop tumours over time. This was not observed in the lab growth derived from gingival tissue.
However, when the stem cells were induced to develop osteoblasts or bone cells, or adipose tissue, the ability declined with the increasing age of the donor. Only in the regeneration of neuronal cells, stem cells derived from gingival tissue were uniformly effective, despite age differences.
And how did the team track this? Dr Tomar says that in bone cells the level of calcium and phosphate keeps rising with the creation of new cells, while in adipose tissue the stem cells become filled with fat globules, which were monitored.
In the paper published this year, the team suggested that these stem cells likely retained their neuronal differentiation ability [to turn into nerve cells of different types). They also said that an autologous stem cell therapy (treatment using one’s own stem cell) for age-related neurodegenerative diseases such as Parkinson’s and Alzheimer’s would be ideal.
Allogeneic therapy involves the use of donated stem cells. “In autologous therapy, chances of rejection of cells or other complications associated with allogeneic transplantation can be avoided,” she says.
Interestingly, the team expanded the experiment to see if stem cell-induced regeneration can help reverse lung damage due to Covid-19 infection. Some studies in Japan as well as Korea used samples from stem cell banks to show that regenerative therapy worked in Covid-19 patients. “Those studies were preliminary, so we expanded our study to review results with stem cells derived from gingiva in autologous therapy for Covid-19 patients.”
The team injected mice with lipopolysaccharides (LPS), which are bacterial cell wall components that replicate bacterial infection. Once LPS populated the lungs of the mice, immune system cells went into overdrive to get rid of them.
Though the team did not inject mice with the Covid-19 virus, the approach helped replicate the inflammation caused in lungs.
(The team separated the mice into two groups and treated one with gingival stem cells.)
The mice that were not injected with stem cells showed up to 60 per cent lung damage within 5-6 days. “There was bleeding and clotting inside the lung tissues” says Dr Tomar. “Though the inflammatory response did not go down significantly for the group that was administered stem cells, the degeneration in the lungs was less by 50-60 per cent.”
Significantly, the age of the donor — be they young, middle-aged, or old — did not matter. “Tissues from all age groups of donors were able to reduce the damage.”
The team measured improvement in lung condition across eight parameters including presence of blood clots and fibroids, and the infiltration of immune cells into the lungs.
Though the team studied the results for four days, it suggests 2-3 rounds of stem cell administration for significant improvement in Covid-19 patients.
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