Healthcare analytics, AI solutions for biological big data, providing an AI platform for the biotech, life sciences, medical and pharmaceutical industries, as well as for related technological approaches, i.e., curation and text analysis with machine learning and other activities related to AI applications to these industries.
Protein Switches: The Programmable Future of Bio-therapeutics
Curator: Dr. Sudipta Saha, Ph. D.
A PNAS paper entitled “A protein therapeutic modality founded on molecular regulation” presents a pioneering approach to creating protein switches—engineered enzymes that activate only in specific molecular environments. This design introduces a new class of context-dependent therapeutics for precision medicine.
Using domain-insertion techniques, researchers inserted ligand-binding domains into scaffold proteins like β-lactamase. These proteins remain inactive until encountering a specific small molecule, which triggers a conformational change and restores enzymatic activity. This offers precise spatiotemporal control—ideal for minimizing off-target effects.
One key innovation is the systematic insertional mutagenesis that identifies functional switch sites across the protein scaffold. This enables the construction of vast protein libraries, increasing the likelihood of finding optimal switch configurations. Furthermore, the approach is modular—different binding domains and enzymes can be combined to create switches tailored to specific clinical contexts.
These smart proteins can be programmed to respond to cancer biomarkers, metabolite levels, or disease-specific molecular cues. By activating only under disease conditions, they provide a blueprint for next-generation bio-therapeutics—potent, selective, and safer.
The method also opens avenues for drug delivery systems, diagnostics, and biosensors, where conditional activation is critical. Overall, this work represents a conceptual leap in synthetic biology and bioengineering, with implications spanning oncology, infectious disease, and regenerative medicine.
Immuno-Timebombs: The Hidden Drivers of Age-Related Illness
Curator: Dr. Sudipta Saha, Ph. D.
There are two converging biological processes that drive most age-related diseases: immunosenescence and inflammaging. Together, they explain how a deteriorating immune system and chronic low-grade inflammation contribute to neurodegenerative diseases, cancer, cardiovascular disorders, and frailty.
Immunosenescence refers to the waning competence of both innate and adaptive immune systems. With age, T and B cells become less effective, and macrophage function declines. This makes older individuals more susceptible to infections and less efficient at clearing dysfunctional cells.
Inflammaging, on the other hand, is the persistent presence of inflammation without infection. Factors like gut microbiome alterations, senescent cell accumulation, and epigenetic drift contribute to this condition. Over time, this “silent fire” damages tissues and lays the groundwork for disease.
These drivers don’t just correlate with disease—they often precede it. This positions inflammaging and immunosenescence as targets for prevention, not just treatment. Interventions like exercise, caloric modulation, and anti-inflammatory diets may attenuate their effects. Emerging therapies such as senolytics and immune rejuvenation approaches (e.g., thymic regeneration) are showing promise.
This article also calls for a paradigm shift in medical science—from reactive disease management to proactive longevity interventions. As we unravel the biological clocks of aging, strategies targeting immune recalibration may delay or prevent multiple diseases simultaneously.
The future of healthy aging may well depend on how early we can intervene in this immuno-inflammatory loop—before pathology sets in.
SNU-BioTalk 2025: Symphony of Cellular Signals in Metabolism and Immune Response – International Conference at Sister Nivedita University, Kolkata, India on 16 & 17 January 2025
Joint Convenor: Dr. Sudipta Saha (Member of LPBI since 2012)
About the Conference:
The International Conference on ‘Symphony of Cellular Signals in Metabolism and Immune Response’ focuses on the complex signalling pathways governing cellular functions in health and disease. It will explore the cellular mechanisms that regulate metabolism, immune responses, and survival, highlighting advances in medical science and biotechnology. Bringing together leading experts and emerging researchers, the conference will feature keynote lectures, panel discussions, research presentations, and interactive sessions, all designed to foster collaboration and innovation. By promoting an exchange of ideas, the event aims to drive transformative insights and solutions that impact human health and sustainable healthcare practices.
The conference will also be livestreamed on YouTube and Facebook
This programme will also host I-STEM: Indian Science, Technology and Engineering facilities Map (I-STEM) is a dynamic and interactive national portal for research cooperation.
Thrust areas:
Intracellular signalling processes of cellular metabolism
Signalling pathways in physiological and pathological processes
Regulatory T cells (Tregs) are important for sperm tolerance and male fertility
Reporter and Curator: Dr. Sudipta Saha, Ph.D.
Regulatory T cells (Tregs) are specialized immune cells that modulate tissue homeostasis. They are a specialized subset of T lymphocytes that function as suppressive immune cells and inhibit various elements of immune response in vitro and in vivo. While there are constraints on the number or function of Tregs which can be exploited to evoke an effective anti-tumor response, sufficient expansion of Tregs is essential for successful organ transplantation and for promoting tolerance of self and foreign antigens. Current studies have provided evidence that a defect in the number or function of Tregs contributes to the etiology of several reproductive diseases.
In the male reproductive tract, prevention of autoimmune responses against antigenic spermatozoa, while ensuring protection against stressors, is a key determinant of fertility. Using an autoimmunity-induced model, it was uncovered that the role of Tregs in maintaining the tolerogenic state of the testis and epididymis. The loss of tolerance induced an exacerbated immune cell infiltration and the development of anti-sperm antibodies, which caused severe male subfertility. By identifying immunoregulatory mechanisms in the testis and epididymis.
Tregs modulate tissue homeostatic processes and immune responses. Understanding tissue-Treg biology will contribute to developing precision-targeting treatment strategies. Here, it was reported that Tregs maintain the tolerogenic state of the testis and epididymis, where sperm are produced and mature. It was found that Treg depletion induces severe autoimmune orchitis and epididymitis, manifested by an exacerbated immune cell infiltration [CD4 T cells, monocytes, and mononuclear phagocytes (MPs)] and the development of anti-sperm antibodies (ASA).
In Treg-depleted mice, MPs increased projections toward the epididymal lumen as well as invading the lumen. ASA-bound sperm enhance sperm agglutination and might facilitate sperm phagocytosis. Tolerance breakdown impaired epididymal epithelial function and altered extracellular vesicle cargo, both of which play crucial roles in the acquisition of sperm fertilizing ability and subsequent embryo development. The affected mice had reduced sperm number and motility and severe fertility defects.
Deciphering these immunoregulatory mechanisms may lead to the development of therapies for infertility and identifying potential targets for immuno-contraception. Ultimately, such knowledge fills gaps related to reproductive mucosa, which is an understudied facet of human male health.
Eight Subcellular Pathologies driving Chronic Metabolic Diseases – Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics: Impact on Pharmaceuticals in Use
In this curation we wish to present two breaking through goals:
Goal 1:
Exposition of a new direction of research leading to a more comprehensive understanding of Metabolic Dysfunctional Diseases that are implicated in effecting the emergence of the two leading causes of human mortality in the World in 2023: (a) Cardiovascular Diseases, and (b) Cancer
Goal 2:
Development of Methods for Mapping Bioelectronic Adjustable Measurements as potential new Therapeutics for these eight subcellular causes of chronic metabolic diseases. It is anticipated that it will have a potential impact on the future of Pharmaceuticals to be used, a change from the present time current treatment protocols for Metabolic Dysfunctional Diseases.
According to Dr. Robert Lustig, M.D, an American pediatric endocrinologist. He is Professor emeritus of Pediatrics in the Division of Endocrinology at the University of California, San Francisco, where he specialized in neuroendocrinology and childhood obesity, there are eight subcellular pathologies that drive chronic metabolic diseases.
These eight subcellular pathologies can’t be measured at present time.
In this curation we will attempt to explore methods of measurement for each of these eight pathologies by harnessing the promise of the emerging field known as Bioelectronics.
Unmeasurable eight subcellular pathologies that drive chronic metabolic diseases
Glycation
Oxidative Stress
Mitochondrial dysfunction [beta-oxidation Ac CoA malonyl fatty acid]
Insulin resistance/sensitive [more important than BMI], known as a driver to cancer development
Membrane instability
Inflammation in the gut [mucin layer and tight junctions]
Epigenetics/Methylation
Autophagy [AMPKbeta1 improvement in health span]
Diseases that are not Diseases: no drugs for them, only diet modification will help
Image source
Robert Lustig, M.D. on the Subcellular Processes That Belie Chronic Disease
These eight Subcellular Pathologies driving Chronic Metabolic Diseases are becoming our focus for exploration of the promise of Bioelectronics for two pursuits:
Will Bioelectronics be deemed helpful in measurement of each of the eight pathological processes that underlie and that drive the chronic metabolic syndrome(s) and disease(s)?
IF we will be able to suggest new measurements to currently unmeasurable health harming processes THEN we will attempt to conceptualize new therapeutic targets and new modalities for therapeutics delivery – WE ARE HOPEFUL
In the Bioelecronics domain we are inspired by the work of the following three research sources:
Michael Levin is an American developmental and synthetic biologist at Tufts University, where he is the Vannevar Bush Distinguished Professor. Levin is a director of the Allen Discovery Center at Tufts University and Tufts Center for Regenerative and Developmental Biology. Wikipedia
THE VOICE of Dr. Justin D. Pearlman, MD, PhD, FACC
PENDING
THE VOICE of Stephen J. Williams, PhD
Ten TakeAway Points of Dr. Lustig’s talk on role of diet on the incidence of Type II Diabetes
25% of US children have fatty liver
Type II diabetes can be manifested from fatty live with 151 million people worldwide affected moving up to 568 million in 7 years
A common myth is diabetes due to overweight condition driving the metabolic disease
There is a trend of ‘lean’ diabetes or diabetes in lean people, therefore body mass index not a reliable biomarker for risk for diabetes
Thirty percent of ‘obese’ people just have high subcutaneous fat. the visceral fat is more problematic
there are people who are ‘fat’ but insulin sensitive while have growth hormone receptor defects. Points to other issues related to metabolic state other than insulin and potentially the insulin like growth factors
At any BMI some patients are insulin sensitive while some resistant
Visceral fat accumulation may be more due to chronic stress condition
Fructose can decrease liver mitochondrial function
A methionine and choline deficient diet can lead to rapid NASH development
Genetic variation causes human lupus, systemic lupus erythematosus (SLE)
Reporter: Aviva Lev-Ari, PhD, RN
TLR7 gain-of-function genetic variation causes human lupus
Abstract
Although circumstantial evidence supports enhanced Toll-like receptor 7 (TLR7) signalling as a mechanism of human systemic autoimmune disease1,2,3,4,5,6,7, evidence of lupus-causing TLR7 gene variants is lacking. Here we describe human systemic lupus erythematosus caused by a TLR7 gain-of-function variant. TLR7 is a sensor of viral RNA8,9 and binds to guanosine10,11,–12. We identified a de novo, previously undescribed missense TLR7Y264H variant in a child with severe lupus and additional variants in other patients with lupus. The TLR7Y264H variant selectively increased sensing of guanosine and 2′,3′-cGMP10,11,12, and was sufficient to cause lupus when introduced into mice. We show that enhanced TLR7 signalling drives aberrant survival of B cell receptor (BCR)-activated B cells, and in a cell-intrinsic manner, accumulation of CD11c+ age-associated B cells and germinal centre B cells. Follicular and extrafollicular helper T cells were also increased but these phenotypes were cell-extrinsic. Deficiency of MyD88 (an adaptor protein downstream of TLR7) rescued autoimmunity, aberrant B cell survival, and all cellular and serological phenotypes. Despite prominent spontaneous germinal-centre formation in Tlr7Y264H mice, autoimmunity was not ameliorated by germinal-centre deficiency, suggesting an extrafollicular origin of pathogenic B cells. We establish the importance of TLR7 and guanosine-containing self-ligands for human lupus pathogenesis, which paves the way for therapeutic TLR7 or MyD88 inhibition.
SOURCE
Brown, G.J., Cañete, P.F., Wang, H. et al.TLR7 gain-of-function genetic variation causes human lupus. Nature605, 349–356 (2022). https://doi.org/10.1038/s41586-022-04642-z
An international team of researchers has identified DNA mutations in a gene that senses viral RNA, as a cause of the autoimmune disease lupus, with the finding paving the way for the development of new treatments.
Lupus is a chronic autoimmune disease which causes inflammation in organs and joints, affects movement and the skin, and causes fatigue. In severe cases, symptoms can be debilitating and complications can be fatal.
In their genetic analysis, carried out at the Centre for Personalised Immunology at the Australian National University, the researchers found a single point mutation in the TLR7 gene. Via referrals from the US and the China Australia Centre of Personalised Immunology (CACPI) at Shanghai Renji Hospital, they identified other cases of severe lupus where this gene was also mutated.
To confirm that the mutation causes lupus, the team used CRISPR gene-editing to introduce it into mice. These mice went on to develop the disease and showed similar symptoms, providing evidence that the TLR7 mutation was the cause. The mouse model and the mutation were both named ‘kika’ by Gabriela, the young girl central to this discovery.
“While it may only be a small number of people with lupus who have variants in TLR7 itself, we do know that many patients have signs of overactivity in the TLR7 pathway. By confirming a causal link between the gene mutation and the disease, we can start to search for more effective treatments.”
The work may also help explain why lupus is about 10 times more frequent in females than in males. As TLR7 sits on the X chromosome, females have two copies of the gene while males have one. Usually, in females one of the X chromosomes is inactive, but in this section of the chromosome, silencing of the second copy is often incomplete. This means females with a mutation in this gene can have two functioning copies.
“There are other systemic autoimmune diseases, like rheumatoid arthritis and dermatomyositis, which fit within the same broad family as lupus. TLR7 may also play a role in these conditions.”
Actemra, immunosuppressive which was designed to treat rheumatoid arthritis but also approved in 2017 to treat cytokine storms in cancer patients SAVED the sickest of all COVID-19 patients
Al is on the way to lead critical ED decisions on CT
Curator and Reporter: Dr. Premalata Pati, Ph.D., Postdoc
Artificial intelligence (AI) has infiltrated many organizational processes, raising concerns that robotic systems will eventually replace many humans in decision-making. The advent of AI as a tool for improving health care provides new prospects to improve patient and clinical team’s performance, reduce costs, and impact public health. Examples include, but are not limited to, automation; information synthesis for patients, “fRamily” (friends and family unpaid caregivers), and health care professionals; and suggestions and visualization of information for collaborative decision making.
In the emergency department (ED), patients with Crohn’s disease (CD) are routinely subjected to Abdomino-Pelvic Computed Tomography (APCT). It is necessary to diagnose clinically actionable findings (CAF) since they may require immediate intervention, which is typically surgical. Repeated APCTs, on the other hand, results in higher ionizing radiation exposure. The majority of APCT performance guidance is clinical and empiric. Emergency surgeons struggle to identify Crohn’s disease patients who actually require a CT scan to determine the source of acute abdominal distress.
Aid seems to be on the way. Researchers employed machine learning to accurately distinguish these sufferers from Crohn’s patients who appear with the same complaint but may safely avoid the recurrent exposure to contrast materials and ionizing radiation that CT would otherwise wreak on them.
Retrospectively, Jacob Ollech and his fellow researcher have analyzed 101 emergency treatments of patients with Crohn’s who underwent abdominopelvic CT.
They were looking for examples where a scan revealed clinically actionable results. These were classified as intestinal blockage, perforation, intra-abdominal abscess, or complex fistula by the researchers.
On CT, 44 (43.5 %) of the 101 cases reviewed had such findings.
Ollech and colleagues utilized a machine-learning technique to design a decision-support tool that required only four basic clinical factors to test an AI approach for making the call.
The approach was successful in categorizing patients into low- and high-risk groupings. The researchers were able to risk-stratify patients based on the likelihood of clinically actionable findings on abdominopelvic CT as a result of their success.
Ollech and co-authors admit that their limited sample size, retrospective strategy, and lack of external validation are shortcomings.
Moreover, several patients fell into an intermediate risk category, implying that a standard workup would have been required to guide CT decision-making in a real-world situation anyhow.
Consequently, they generate the following conclusion:
We believe this study shows that a machine learning-based tool is a sound approach for better-selecting patients with Crohn’s disease admitted to the ED with acute gastrointestinal complaints about abdominopelvic CT: reducing the number of CTs performed while ensuring that patients with high risk for clinically actionable findings undergo abdominopelvic CT appropriately.
Main Source:
Konikoff, Tom, Idan Goren, Marianna Yalon, Shlomit Tamir, Irit Avni-Biron, Henit Yanai, Iris Dotan, and Jacob E. Ollech. “Machine learning for selecting patients with Crohn’s disease for abdominopelvic computed tomography in the emergency department.” Digestive and Liver Disease (2021). https://www.sciencedirect.com/science/article/abs/pii/S1590865821003340
Other Related Articles published in this Open Access Online Scientific Journal include the following:
Effective humoral immune responses to infection and immunization are defined by high-affinity antibodies generated as a result of B cell differentiation and selection that occurs within germinal centers (GC). Within the GC, B cells undergo affinity maturation, an iterative and competitive process wherein B cells mutate their immunoglobulin genes (somatic hypermutation) and undergo clonal selection by competing for T cell help. Balancing the decision to remain within the GC and continue participating in affinity maturation or to exit the GC as a plasma cell (PC) or memory B cell (MBC) is critical for achieving optimal antibody avidity, antibody quantity, and establishing immunological memory in response to immunization or infection. Humoral immune responses during chronic infections are often dysregulated and characterized by hypergammaglobulinemia, decreased affinity maturation, and delayed development of neutralizing antibodies. Previous studies have suggested that poor antibody quality is in part due to deletion of B cells prior to establishment of the GC response.
In fact the impact of chronic infections on B cell fate decisions in the GC remains poorly understood. To address this question, researchers used single-cell transcriptional profiling of virus-specific GC B cells to test the hypothesis that chronic viral infection disrupted GC B cell fate decisions leading to suboptimal humoral immunity. These studies revealed a critical GC differentiation checkpoint that is disrupted by chronic infection, specifically at the point of dark zone re-entry. During chronic viral infection, virus-specific GC B cells were shunted towards terminal plasma cell (PC) or memory B cell (MBC) fates at the expense of continued participation in the GC. Early GC exit was associated with decreased B cell mutational burden and antibody quality. Persisting antigen and inflammation independently drove facets of dysregulation, with a key role for inflammation in directing premature terminal GC B cell differentiation and GC exit. Thus, the present research defines GC defects during chronic viral infection and identify a critical GC checkpoint that is short-circuited, preventing optimal maturation of humoral immunity.
Together, these studies identify a key GC B cell differentiation checkpoint that is dysregulated during chronic infection. Further, it was found that the chronic inflammatory environment, rather than persistent antigen, is sufficient to drive altered GC B cell differentiation during chronic infection even against unrelated antigens. However, the data also indicate that inflammatory circuits are likely linked to perception of antigen stimulation. Nevertheless, this study reveals a B cell-intrinsic program of transcriptional skewing in chronic viral infection that results in shunting out of the cyclic GC B cell process and early GC exit with consequences for antibody quality and hypergammaglobulinemia. These findings have implications for vaccination in individuals with pre-existing chronic infections where antibody responses are often ineffective and suggest that modulation of inflammatory pathways may be therapeutically useful to overcome impaired humoral immunity and foster affinity maturation during chronic viral infections.
4.1.8 Newly Found Functions of B Cell, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 4: Single Cell Genomics
The importance of B cells to human health is more than what is already known. Vaccines capable of eradicating disease activate B cells, cancer checkpoint blockade therapies are produced using B cells, and B cell deficiencies have devastating impacts. B cells have been a subject of fascination since at least the 1800s. The notion of a humoral branch to immunity emerged from the work of and contemporaries studying B cells in the early 1900s.
Efforts to understand how we could make antibodies from B cells against almost any foreign surface while usually avoiding making them against self, led to Burnet’s clonal selection theory. This was followed by the molecular definition of how a diversity of immunoglobulins can arise by gene rearrangement in developing B cells. Recombination activating gene (RAG)-dependent processes of V-(D)-J rearrangement of immunoglobulin (Ig) gene segments in developing B cells are now known to be able to generate an enormous amount of antibody diversity (theoretically at least 1016 possible variants).
With so much already known, B cell biology might be considered ‘‘done’’ with only incremental advances still to be made, but instead, there is great activity in the field today with numerous major challenges that remain. For example, efforts are underway to develop vaccines that induce broadly neutralizing antibody responses, to understand how autoantigen- and allergen-reactive antibodies arise, and to harness B cell-depletion therapies to correct non-autoantibody-mediated diseases, making it evident that there is still an enormous amount we do not know about B cells and much work to be done.
Multiple self-tolerance checkpoints exist to remove autoreactive specificities from the B cell repertoire or to limit the ability of such cells to secrete autoantigen-binding antibody. These include receptor editing and deletion in immature B cells, competitive elimination of chronically autoantigen binding B cells in the periphery, and a state of anergy that disfavors PC (plasma cell) differentiation. Autoantibody production can occur due to failures in these checkpoints or in T cell self-tolerance mechanisms. Variants in multiple genes are implicated in increasing the likelihood of checkpoint failure and of autoantibody production occurring.
Autoantibodies are pathogenic in a number of human diseases including SLE (Systemic lupus erythematosus), pemphigus vulgaris, Grave’s disease, and myasthenia gravis. B cell depletion therapy using anti-CD20 antibody has been protective in some of these diseases such as pemphigus vulgaris, but not others such as SLE and this appears to reflect the contribution of SLPC (Short lived plasma cells) versus LLPC (Long lived plasma cells) to autoantibody production and the inability of even prolonged anti-CD20 treatment to eliminate the later. These clinical findings have added to the importance of understanding what factors drive SLPC versus LLPC development and what the requirements are to support LLPCs.
B cell depletion therapy has also been efficacious in several other autoimmune diseases, including multiple sclerosis (MS), type 1 diabetes, and rheumatoid arthritis (RA). While the potential contributions of autoantibodies to the pathology of these diseases are still being explored, autoantigen presentation has been posited as another mechanism for B cell disease-promoting activity.
In addition to autoimmunity, B cells play an important role in allergic diseases. IgE antibodies specific for allergen components sensitize mast cells and basophils for rapid degranulation in response to allergen exposures at various sites, such as in the intestine (food allergy), nose (allergic rhinitis), and lung (allergic asthma). IgE production may thus be favored under conditions that induce weak B cell responses and minimal GC (Germinal center) activity, thereby enabling IgE+ B cells and/or PCs to avoid being outcompeted by IgG+ cells. Aside from IgE antibodies, B cells may also contribute to allergic inflammation through their interactions with T cells.
B cells have also emerged as an important source of the immunosuppressive cytokine IL-10. Mouse studies revealed that B cell-derived IL-10 can promote recovery from EAE (Experimental autoimmune encephalomyelitis) and can be protective in models of RA and type 1 diabetes. Moreover, IL-10 production from B cells restrains T cell responses during some viral and bacterial infections. These findings indicate that the influence of B cells on the cytokine milieu will be context dependent.
The presence of B cells in a variety of solid tumor types, including breast cancer, ovarian cancer, and melanoma, has been associated in some studies with a positive prognosis. The mechanism involved is unclear but could include antigen presentation to CD4 and CD8 T cells, antibody production and subsequent enhancement of presentation, or by promoting tertiary lymphoid tissue formation and local T cell accumulation. It is also noteworthy that B cells frequently make antibody responses to cancer antigens and this has led to efforts to use antibodies from cancer patients as biomarkers of disease and to identify immunotherapy targets.
Malignancies of B cells themselves are a common form of hematopoietic cancer. This predilection arises because the gene modifications that B cells undergo during development and in immune responses are not perfect in their fidelity, and antibody responses require extensive B cell proliferation. The study of B cell lymphomas and their associated genetic derangements continues to be illuminating about requirements for normal B cell differentiation and signaling while also leading to the development of targeted therapies.
Overall this study attempted to capture some of the advances in the understanding of B cell biology that have occurred since the turn of the century. These include important steps forward in understanding how B cells encounter antigens, the co-stimulatory and cytokine requirements for their proliferation and differentiation, and how properties of the B cell receptor, the antigen, and helper T cells influence B cell responses. Many advances continue to transform the field including the impact of deep sequencing technologies on understanding B cell repertoires, the IgA-inducing microbiome, and the genetic defects in humans that compromise or exaggerate B cell responses or give rise to B cell malignancies.
Other advances that are providing insight include:
single-cell approaches to define B cell heterogeneity,
glycomic approaches to study effector sugars on antibodies,
new methods to study human B cell responses including CRISPR-based manipulation, and
the use of systems biology to study changes at the whole organism level.
With the recognition that B cells and antibodies are involved in most types of immune response and the realization that inflammatory processes contribute to a wider range of diseases than previously believed, including, for example, metabolic syndrome and neurodegeneration, it is expected that further
basic research-driven discovery about B cell biology will lead to more and improved approaches to maintain health and fight disease in the future.
Will Lab-Grown Insulin-Producing Cells be the Next Insulin Pill?
Reporter: Irina Robu, PhD
Type 1 diabetes is an autoimmune disorder that destroys the insulin-producing beta cells of the pancreas, typically in childhood. Starved of insulin’s ability to regulate glucose levels in the blood, spikes in blood sugar can cause serious organ damage and eventually death. Replacing insulin cells lost in patients with Type 1 diabetes, has been a goal in regenerative medicine, but until now researchers had not been able to figure out how to produce cells in a lab dish that work as they do in healthy adults.
Dr. Matthias Hebrok, director of Diabetes Center at UCSF published a study on Feb 1, 2019 in Nature Cell Biology looked into generating insulin-producing cells that look and act a lot like the pancreatic beta cell. Hebrok and colleagues replicated the physical process by which the cells separate from the rest of the pancreas and form the so-called islets of Langerhans in the lab.
When the researchers replicated that process in lab dishes by artificially separating partially differentiated pancreatic stem cells and reforming them into islet-like clusters, the cells’ development unexpectedly leap forward. Not only did the beta cells begin responding to blood sugar more like mature insulin-producing cells, but similarly appeared to develop in ways that had never been realized in a laboratory setting. The scientist then transplanted these lab-grown islets into healthy mice and found that that in a matter of days, they produce more insulin than the animals’ own islets.
In partnership with bioengineers, geneticists, and other colleagues at UCSF, Hebrok’s team is by now working to move regenerative therapies to reality by using CRISPR gene editing to make these cells transplantable into patients without the necessity for immune-suppressing drugs or by screening drugs that could reinstate proper islet function in patients with Type 1 diabetes by protecting and expanding the few remaining beta cells to restart pancreatic insulin production.
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