September 22, 2020

The Niche

Knoepfler lab stem cell blog

Recommended regenerative medicine reads: COVID-19 updates, Cornea Fix, Pubs

Another week and more great papers and interesting news in the regenerative medicine sphere including COVID-19 updates, stem cells for vision, and more.

Rebuilding Corneas With Stem Cells

Stem cell-based regenerative medicine arguably has shown the most promise for vision loss. A PR from Massachusetts Eye and Ear says: Doctors rebuild damaged corneas using patients’ own own stem cells for first time in US.

This is interesting work.

The autologous transplant method is called “‘cultivated autologous limbal epithelial cell transplantation’ (CALEC).” It involves taking a biopsy, culturing a mixture of the cells including stem cells, and then a transplant back. Here is the Clinicaltrials.gov listing if you want to learn more.

COVID updates

1. Mesoblast DSMB gives nod to continue trial; how much does this mean?

Mesoblast is upbeat in PR Data Safety Monitoring Board Recommends Continuation of Remestemcel-L Phase 3 Trial in COVID-19 Patients With Acute Respiratory Distress Syndrome. I’m not clear how much to read into this news on stem cells for COVID-19. Is the data safety monitoring board just saying the safety has been OK so far or do they see any hint of efficacy?

In either case, it’s encouraging to some extent that this work will continue.

2. IPS cells to model COVID infection reveals cardiac phenotypes

2019nCoV NP cardio myocytes
The novel coronavirus can infect human cardiomyocytes. Marchiano, et al. 2020 preprint. Fig 2 (b) Immunofluorescent staining of H7 hESC-CMs and WTC11c hiPSC-CMs at 48 HPI with SARS-CoV-2 dose of 0.1 MOI. Scale bars: 50 μm.

A preprint from the UW ISCRM from Chuck Murry‘s group: SARS-CoV-2 infects human pluripotent stem cell-derived cardiomyocytes, impairing electrical and mechanical function. This highlights the power of human IPS cells for disease modeling. It’s still sort of a neck and neck race as to whether IPS cells will have greater clinical impact directly (e.g. via transplant of differentiated cells made from IPS cells) or by disease modeling.

I asked first author Silvia Marchiano of the UW ISCRM for the main takeaways from the study:

” I think that the most important take-home messages are: 1) the cardiac effects seen with COVID19 patients could be directly mediated by the virus, independently from inflammation or coagulation disorders 2) since the heart is a non regenerative organ, we should consider the potential long term effects of this infection. Of course, more studies are needed to confirm the cardiac tropism of nCoV2 but the evidence so far suggests that nCoV2 could be a cardiac virus and understanding which patients are at higher risk and what are the potential consequences are definitely the next steps.”

3. UCSF Stem Cells for COVID trial

From UCSF PR: Stem Cell Trial Tests Treatment for Often-Fatal COVID-19 Lung Damage

“Researchers are studying whether cells drawn from deep inside our bones may hold hope for the sickest of COVID-19 patients who have severe lung injury called acute respiratory distress syndrome, or ARDS.”

The trial will include multiple sites including here at UC Davis School of Medicine.

4. Mice catching COVID

Studies show that a common mouse can catch and spread the coronavirus in labs

More on Cryo negatively impacting stem cells

From ASH, Study: Cryopreservation Associated with Loss of Quality in Donor Stem Cell Products. I also had a recent piece on the effects of freeze-thaw on stem cells here.

Childhood Cancer Fundraiser

My lab here at UC Davis and our colleagues at the UC Davis Comprehensive Cancer Center have a fundraising team for Alex’s Lemonade Stand Foundation. We raising money by walking, jogging and/or biking. The money gets matched 1:1 by the foundation and goes to our work on childhood brain tumors. Please consider joining our team or making a contribution. Everything helps! Alex’s Lemonade Stand Foundation is an amazing organization.

Han et al PNAS 2020 Fig 7a
“Representative images of hippocampus electroporated at E15 and collected at P10 showing control (GFP) (A), CUL5 KD (shCUL5)” from Han et al PNAS 2020 , Figure 7a.

Recommended stem cell and regenerative medicine pubs, preprints

Blast from the Past: contagious cancer

From January 2011: Contagious cancer: the allograft your dog doesn’t want