The human eye, which contains stem cells that are vulnerable to sleep deprivation, new studies show. Credit: Unsplash.
“Regenerative medicine news under the microscope” is a monthly feature highlighting big stories in stem cell research. I will sample the latest and greatest findings in recent press and package them into a single post.
April was full of great research and big headlines, so this month I’ve prepared a rapid-fire edition of the blog. A few more stories and slightly shorter summaries. I cover more new work on the molecular mechanisms of COVID-19, the effects of sleep deprivation on your corneal stem cells, de-aged skin cells, and more!
Pick of the Month
The adverse effects of sleep deprivation on corneal stem cells
Getting a decent night’s sleep can be difficult for a multitude of reasons. In fact, one in 3-4 Canadian adults don’t sleep enough. This month, Li et al. tack on yet another reason why sleep should be a priority. In mice, short-term sleep deprivation resulted in negative effects on the tear film, including increased reactive oxygen species and a drop in local anti-oxidant levels. In addition, excessive stem cell proliferation in the cornea was also observed. These effects were remedied by eye drops containing antioxidants, which is good news. Conversely, long-term deprivation resulted in more serious effects, such as corneal thinning, loss of transparency, and a reduction in stem cell populations. The authors warn that, in the long run, this could lead to vision impairments, though further studies will be required to confirm this.
Preclinical promise in hemophilia A study
This month, Gage et al. tackle hemophilia A, a heritable blood disorder marked by the lack of an important clotting factor. The team generated liver blood vessel cells from human pluripotent stem cells, and transplanted them into immunocompromised mice with hemophilia A. The cells engrafted, proliferated and matured, ultimately correcting the bleeding pathology. Read more in Cell Reports, or this UHN press release.
The de-aged skin paper everyone’s been talking about
The goal: to restore youth to the epigenome of a cell, without completely reprogramming it to become a stem cell. Enter “maturation phase transient reprogramming,” or MPTR for short, a new method published by Gill et al. in eLife this month. A specific set of factors are expressed for a limited period of time before removal, leading to rejuvenation. Testing the technique on dermal fibroblasts sourced from donors that were middle-aged left cells 30 years younger with regard to their transcriptomes, as measured using a “novel transcriptome clock.” Don’t miss this read and also have a look at blogger Krystal Jacques’ in-depth review in ”The science behind the headlines: Turning back the clock on skin cells.”
Chemical reprogramming: Small molecules in the pursuit of stemness
Chemical reprogramming has been tapped as a solution to issues with more established reprogramming techniques, such as a potential reduction in the risk of tumorigenesis during the process, and elimination of the need for viral vectors used in protocols to express transgenes. Though it’s been achieved in mice, small molecules had yet to be applied successfully in human reprogramming endeavours – until now. Bookmark this paper by Guan et al. in Nature.
Another COVID double-feature: Findings on macrophages, pericytes
Trying to determine why some COVID-19 patients present with more severe inflammatory conditions than others, the authors of this first study use human pluripotent stem cell-derived macrophages and lung cells to examine immune response patterns in different macrophage subtypes, making correlations to disease severity.
In the second paper, expression of ACE2 – the receptor SARS-CoV-2 binds to – is mapped across multiple mouse organs, through postnatal development and adulthood, to pin down potential viral entry points into the tissue via the vasculature. These mapping efforts are important given that humanized mouse models are being used more frequently in COVID-19 research (standard laboratory mice cannot be infected), so a more detailed understanding is needed.
A new multi-organ chip with built-in vascular flow
Ronaldson-Bouchard et al. have developed a multi-organ chip that allows for free communication between tissue types to represent the physiology of the whole more accurately. Their system contains mature heart, skin, liver and bone tissue, with specially designed vascular flow to facilitate inter-organ chemical communication. To read more about this new chip and everything the authors were able to do with it, head over to Nature Biomedical Engineering.
More crying organoids!
You may remember the first ever blog from this series, back in April of last year, where I covered crying lacrimal gland organoids by Bannier-Hélaouët et al. Here, we have new human lacrimal gland organoids that form beautiful branching structures in vitro. They were found to functionally mature when transplanted into rats and produce tear film products, which protect the eye and facilitate vision. This could hold promise for patients suffering from Sjögren’s syndrome, an autoimmune disease that causes lacrimal land dysfunction and dry eye syndrome.
Additional recommendations
Here are some papers/headlines that I didn’t have room for above:
Single cell analyses identify a highly regenerative and homogenous human CD34+ hematopoietic stem cell population. Anjos-Afonso et al. in Nature Communications.
Cell-lineage controlled epigenetic regulation in glioblastoma stem cells determines functionally distinct subgroups and predicts patient survival. Lu et al. in Nature Communications.
Maladaptive innate immune training of myelopoiesis links inflammatory comorbidities. Li et al. in Cell.
The creator of the CRISPR babies has been released from a Chinese prison. Antonio Regalado for MIT Technology Review.
Periodic formation of epithelial somites from human pluripotent stem cells. Sanaki-Matsumiya et al. in Nature Communications.
Financial risks posed by unproven cell interventions: Estimation of refunds from medical expense deductions in Japan. Hatta et al. in Stem Cell Reports.
Crispr Pioneer Expects to See Gene-Edited Babies Within 25 Years. Angelica Peebles for Bloomberg.
Neuroglial Senescence, α-Synucleinopathy, and the Therapeutic Potential of Senolytics in Parkinson’s Disease. Miller et al. in Frontiers in Neuroscience.
Progenitor cells from brown adipose tissue undergo neurogenic differentiation. Jumabay et al. in Scientific Reports.
Mapping human haematopoietic stem cells from haemogenic endothelium to birth. Calvanese et al. in Nature.
Investigating the feasibility and ethical implications of phenotypic screening using stem cell-derived tissue models to detect and manage disease. Harris et al. in Stem Cell Reports.
Synthetic antibody–immune cell complex dramatically shrinks blood tumors. Jocelyn Kaiser for Science.
Modelling ciliopathy phenotypes in human tissues derived from pluripotent stem cells with genetically ablated cilia. Cruz et al. in Nature Biomedical Engineering.
Generation of 3D retinal tissue from human pluripotent stem cells using a directed small molecule-based serum-free microwell platform. Rashidi et al. in Scientific Reports.
PPARdelta activation induces metabolic and contractile maturation of human pluripotent stem cell-derived cardiomyocytes. Wickramasinghe et al. in Cell Stem Cell.
Engineered three-dimensional cardiac tissues maturing in a rotating wall vessel bioreactor remodel diseased hearts in rats with myocardial infarction. Nakazato et al. in Stem Cell Reports.
Cell-intrinsic Aryl Hydrocarbon Receptor signalling is required for the resolution of injury-induced colonic stem cells. Shah et al. in Nature Communications.
Calcium phosphate-based biomaterials trigger human macrophages to release extracellular traps. Seifert et al. in Biomaterials.
Functional Recovery from Human Induced Pluripotent Stem Cell-Derived Dopamine Neuron Grafts is Dependent on Neurite Outgrowth. Hills et al. in bioRxiv. Please note that this is a preprint and has not been peer-reviewed.
The nuclear receptor ERR cooperates with the cardiogenic factor GATA4 to orchestrate cardiomyocyte maturation. Sakamoto et al. in Nature Communications.
Biomechanically and biochemically functional scaffold for recruitment of endogenous stem cells to promote tendon regeneration. Cui et al. in npj Regenerative Medicine.
Hub of Regenerative Medicine & Stem Cell Meetings 2022. Paul Knoepfler for The Niche.
Stay tuned for my next post, coming up in May!
Lyla El-Fayomi
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