Understanding Stem Cell Functionality

Proposed mechanism of action of injected stem cells: There is a popular misconception that injected stem cells somehow magically transform into different tissue types, thereby promoting a healing and restorative effect. Patients often believe that injected stem cells will regrow cartilage or other tissue. However, this does not appear to be the case. The venerable late Arnold Caplan PhD, who coined the term "Mesenchymal Stem Cells" (MSC's), later said that we should actually call MSCs "medicinal signaling cells." Less than 5% of injected stem cells actually appear to terminally differentiate into new tissue types. The vast majority of the cells have a paracrine activity, stimulating or activating nascent stem cells living in the underlying tissue and which then begin the healing process. Caplan identified these nascent cells as "pericytes" or perivascular cells. They are present at intervals along the walls of capillaries (and post-capillary venules). They are primarily involved in regulating blood flow. However, Caplan postulated that activated pericytes transform into MSCs that migrate from capillary beds to areas of damage to help promote repair and healing. The attached time-lapse scanning electron micrograph video shows activated pericytes peeling off the capillary and migrating to the site of an epithelial wound in a zebra fish. The bottom line here is that not only is it important that we as clinicians understand the mechanism of action of the treatments that we provide (at least to the best of our current understanding), but also that we are honest with our patients about how these treatments are thought to work so that patients don't have unrealistic expectations. (FYI, I'm honored to have been the inaugural recipient of the Arnold Caplan Award of Excellence in Education, conferred by TOBI/ASIPPS at last year's TOBI symposium.) #MSC #mesenchymal #stem #Cells #perivascular #pericytes #healing #migration

Ever wondered how our cells achieve precise control over gene expression during differentiation, even when master regulatory proteins are expressed in overlapping patterns? 7 notes and all this music! Using 64,400 fully synthetic DNA sequences, Froemel et al. set out to uncover the hidden design principles in blood stem cell differentiation. Three surprising mechanisms allow enhancers to convert broad transcription factor (TF) gradients into highly specific gene expression: Occupancy-Dependent Duality: A single TF motif can act as both an activator and a repressor, simply depending on how much of the TF is predicted to occupy the enhancer. This creates a "filter" for specific TF activity, not just maximal or minimal. Cell-State-Dependent Duality: The same TF motif can be interpreted differently across various cell states, influenced by the cellular environment, co-factors, or post-translational modifications. Combinatorial Duality (The Big Surprise!): Combinations of activating TF binding sites can actually neutralize each other or even become repressive. This "negative synergy" is crucial for converting quantitative imbalances in TF expression into binary (on/off) activity patterns, ensuring mutual exclusivity of stem and progenitor cell programs. These principles allow to design enhancers from scratch with specificity to user-defined hematopoietic progenitor cell states. This work highlights the critical role of pairwise TF interactions in achieving regulatory specificity and offers transparent insights into how cells precisely control their fate. This research challenges previous assumptions, especially given observations in some cancer cell lines, and provides a foundational understanding of gene regulation in primary blood progenitors. #GeneRegulation #CellDifferentiation #Enhancers #Hematopoiesis #SyntheticBiology #Genomics #TranscriptionFactors #Biotechnology #Immunology #ImmuneCells https://lnkd.in/em-DkjtY

Relationship between stem cells and mechanical signals unveiled! Previously researchers found that PIEZO ion channels influence tumour stiffening in brain cancer. Inspired by this research, the research team set out to explore how stem cells in the intestines use PIEZO channels to stay healthy and function properly. In a preclinical model, the study team knocked out (turned off) PIEZO1 and PIEZO2 in the intestines. The results were dramatic: in the absence of both PIEZO channels, the stem cells couldn't maintain their necessary functions, leading to severe illness and rapid death. Although these PIEZO channels were previously known to have distinct functions, this study has revealed their unexpected redundancy in stem cell maintenance. The labs identified that PIEZO ion channels were helping stem cells feel physical changes in their surroundings, like how stiff or stretchy the environment is. Without these channels, there was an imbalance in two critical signaling pathways, causing the stem cells to miss important changes in their environment and improperly differentiate. “When PIEZO channels are missing, stem cells can't stay stem cells. Instead, they turn into other cell types too quickly, leading to serious health problems,” says the author. #ScienceMission #sciencenewshighlights https://lnkd.in/g6g8wHqQ