A human T cell, under attack by HIV (yellow). Credit: National Cancer Institute/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.
This month, I cover an advance in the fight against HIV, a sound-based stem cell differentiation strategy, swimming heart cells, and more!
Pick of the Month
Woman cured of HIV thanks to stem cells from resistant donor
We’ve heard about similar cases before: Adam Castillejo and Timothy Brown, the two patients previously cured of HIV, received bone marrow transplants from individuals found to have a genetic mutation preventing HIV infection (read more about that here). This time around, a woman with HIV – whose identity is currently being protected – received umbilical cord blood from a donor with natural HIV resistance and ended up cured. She was originally given this treatment for leukemia, but thanks to strategic donor selection by her doctors, she’s been HIV-free for 14 months now.
Treatment using umbilical cord blood offers a few important advantages over bone marrow transplants; it’s less invasive, more accessible in terms of wider availability, and recipients need not be matched as closely to donors.
This treatment was part of a larger study involving 25 people in total, so it won’t necessarily be made available as a mainstream treatment for HIV just yet; however, it is definitely cause for excitement. Read more at Smithsonian Magazine.
Harnessing the force (of sound) to generate bone
Mesenchymal stem cells (MSCs) make yet another appearance in this study, where Ambattu et al. take advantage of mechanotransduction – the conversion of physical forces to biochemical signals – to induce osteogenic differentiation.
We know that sounds produce vibrations, and that those vibrations are physically detectable elements. We also know that many cell types are equipped with special machinery allowing them to detect and respond to physical forces acting on them. Researchers have taking advantage of this in the context of in vitro bone generation and found that seven days of continuous, low-frequency sound stimulation could cause MSCs to differentiate to osteoblast lineages. In this paper, the authors devise a five-day protocol involving just ten minutes of high-frequency sound stimulation daily. In addition, the small size of the equipment and the relatively low cost make this approach an attractive candidate for adaptation to larger-scale bioreactors. This represents a significant advance in bone regeneration research, which aims to one day find solutions for patients who have lost bone to degenerative diseases or cancer.
A preclinical model of kidney regeneration
In recent years, you’ve likely come across or heard about organ-derived decellularized extracellular matrices (ECMs). These are created by removing all living cells from an organ so that only the structural architecture is left, including vascular networks, signaling molecules and non-cellular physical scaffolding composed of collagen, proteins and other critical components. Experiments involving ECMs have shown great promise in regeneration research over the years, and this story is just another example of this.
We know that our kidneys have a very limited capacity for regeneration, so efforts to promote endogenous repair have been ongoing. In this paper, Tajima et al. repair porcine kidney damage using ECM transplants sutured onto the wound site. It took just 28 days to see results. This was a really interesting read.
Swimming heart cells
To really understand something, experts often advise that you should be able to take it apart completely and put it back together again. This next paper brought that to mind. Lee et al. share their new biohybrid organism – a device containing live, biological components – in Science this month. They created a “fish analog” comprised of a scaffold with muscle grown onto it in such a way that allows it to swim. Despite the fact that the end result was highly entertaining, their research goes far beyond this; the aim was to further our understanding of design and coordination mechanisms in muscle, with the hopes that one day we’ll be able to build functional and sophisticated human hearts in the lab using stem cells.
How does it swim? A bilayer construct, made of cardiac muscle cells that contract and relax reciprocally, produces a tail swish-like motion. They refer to this as stretch-induced antagonistic contraction; to simplify, “muscle A’s” contraction stimulates “muscle B” to contract (and muscle A relaxes to allow for this), resulting in a closed-loop system that’s self-sustaining. I’ve grossly oversimplified what they’ve done, so head over to the source to read more – and make sure to check out their (very cool) videos while you’re there.
A new approach to dopamine neuron transplants for Parkinson’s
Transplanted neurons usually display limited capacity for axonal growth and innervation across long distances, preventing doctors from being able to simply transplant healthy neurons into brain regions where they’re diseased; for instance, this is the case with Parkinson’s disease patients. The wiring of the circuit will be imperfect, as far-away disease-relevant projection sites won’t be connected well enough. To get around this in various studies, neurons are sometimes transplanted close to disease-relevant projection sites. However, when this compromise is made and neurons are put in places they might not be found naturally, only partial functional recovery is achieved.
This month in Cell Stem Cell, Moriarty et al. ask whether or not it’s possible to guide the axonal growth and innervation of transplanted dopaminergic neurons to correct motor dysfunction associated with their ablation, and they do this using a combination of cell and gene therapies. Spoiler alert: they make it happen in rat models, and the results are really something. I highly recommend this read.
Additional recommendations
Here are some papers/headlines that I didn’t have room for above:
Safety and Efficacy of Mesenchymal Stromal Cells and Other Cellular Therapeutics in Rheumatic Diseases in 2022: A review of what we know so far. Gilkeson in Arthritis & Rheumatology.
SARS-CoV-2 Infection and Lung Regeneration. Zhao et al. in Clinical Microbiology Reviews.
Tissue origin of cytotoxic natural killer cells dictates their differential roles in mouse digit tip regeneration and progenitor cell survival. Dastagir et al. in Stem Cell Reports.
BMAL1 drives muscle repair through control of hypoxic NAD+ regeneration in satellite cells. Zhu et al. in Genes & Development.
Human expandable pancreatic progenitor–derived β cells ameliorate diabetes. Ma et al. in Science Advances.
Animal studies for the evaluation of in situ tissue-engineered vascular grafts — a systematic review, evidence map, and meta-analysis. Koch et al. in npj Regenerative Medicine.
Survival of an HLA-mismatched, bioengineered RPE implant in dry age-related macular degeneration. Kashani et al. in Stem Cell Reports.
Coupling comprehensive pesticide-wide association study to iPSC dopaminergic screening identifies and classifies Parkinson-relevant pesticides. Paul et al. on bioRxiv. Please note that this paper has not been peer-reviewed.
How to protect the first ‘CRISPR babies’ prompts ethical debate. Smriti Mallapaty for Nature News.
P53 directs leader cell behavior, migration, and clearance during epithelial repair. Kozyrska et al. in Science.
Single-cell profiling of human subventricular zone progenitors identifies SFRP1 as a target to re-activate progenitors. Donega et al. in Nature Communications.
MBNL1 drives dynamic transitions between fibroblasts and myofibroblasts in cardiac wound healing. Bugg et al. in Cell Stem Cell.
Effective targeting of breast cancer stem cells by combined inhibition of Sam68 and Rad51. Turdo et al. in Oncogene.
YAP signaling in horizontal basal cells promotes the regeneration of olfactory epithelium after injury. Wu et al. in Stem Cell Reports.
Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells. Raina et al. in Development.
SoxD genes are required for adult neural stem cell activation. Li et al. in Cell Reports.
Thymic stromal lymphopoietin controls hair growth. Shannon et al. in Stem Cell Reports.
Metabolic regulation of somatic stem cells in vivo. Meacham et al. in Nature Reviews Molecular Cell Biology.
Decade-long leukaemia remissions with persistence of CD4+ CAR T cells. Melenhorst et al. in Nature.
UC Davis becomes first in region to grow cancer-fighting CAR T cells. UC Davis Health News.
GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Majzner et al. in Nature.
The microbiota regulates hematopoietic stem cell fate decisions by controlling iron availability in bone marrow. Zhang et al. in Cell Stem Cell.
Stay tuned for my next post, coming up in March!
Lyla El-Fayomi
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