At least 10% of the elderly population above the age of 70 carry a condition termed clonal hematopoiesis indeterminate potential (CHIP) due to oligoclonal expansion of mutated hematopoietic stem cells. Although CHIP is known to predispose patients to a higher risk of malignant blood disorders, the recent revelation of its association with higher morbidity and mortality of atherosclerotic cardiovascular disease and ischemic stroke is rather surprising. Two independent research groups published studies indicating that Tet2 mutated monocytes from mice modeling CHIP had a causal role in accelerating the growth of atherosclerotic lesions due to their pro-inflammation activities. This important discovery points to CHIP as a risk factor and raises the prospect of novel treatment to minimize the adverse cardio/cerebro-vascular events.

Obesity is a chronic, complex disease, which is associated with several comorbidities, including diabetes mellitus, hypertension, and cardiovascular diseases. It is estimated that the prevalence of obesity among both adults and children nearly tripled between 1975 and 2016, highlighting a huge unmet treatment need. However, the currently available anti-obesity drugs have serious side effects, which limit their long-term use. The finding that the newly-identified brain GDF15-GFRAL-RET receptor signaling complex is involved in stress/disease-induced anorexia will certainly impact our knowledge of body weight homeostasis under healthy and disease conditions. Based on this breakthrough, a new class of GFRAL/RET-based drugs is highly anticipated for the treatment of obesity, as well as cancer-induced cachexia.

Induced pluripotent stem cells (iPSCs) hold great promise for the treatment of human diseases, including the failure of bone marrow. Incremental progress across the past three and half decades has brought us closer to making hematopoietic stem cells from iPSCs clinical solutions. A recent innovative two-step differentiation approach successfully generated transplantable HSCs from iPSC sources. For clinical translation, the long-term safety of these gene-altered HSCs must be determined.

Induced pluripotent stem cells (iPSCs) hold great promise for the treatment of human diseases. Two recent first-of-its-kind clinical case reports on the iPSC-based treatment of age-related macular degeneration (AMD) highlight the hopes and challenges associated with the clinical application of iPSCs.

iPSCs hold great promise in that a large quantity of cardiomyocytes (iPSC-CM) can be generated and cultured in vitro for clinical purposes. These cells are currently being subjected to vigorous testing in animal transplantation models to ascertain their survivability and functional integration in the injured heart. So far, most of those studies have been conducted in small animals and sometimes in xenogeneic settings, and have produced mixed results. Representing a step forward, a recent study in Nature reported the transplantation of MHC-matched allogeneic monkey iPSC-CM. This was the first time iPSC-CM have been tested in a non-human primate model in an allogeneic setting, which is the next best thing to a human clinical trial.

Two articles recently published in Nature and Nature Cell Biology reported that early human embryos were successfully cultured beyond blastulation. This development heralds an important step toward exploring the unknown molecular events driving human pre-gastrulation development, but it inevitably raises the ante in the decades-old ethical debate on how to define early human life and how to save human lives through research without destroying another life in the process.

The majority of clinical blindness is caused by a loss of transparency of the lens and cornea, largely due to cataracts and corneal injuries. The most common treatment used to restore the transparency is surgical removal of the damaged tissues, followed by transplantation of donated corneal tissue or an artificial lens. However, these therapies are not without limitations or untoward effects. Unraveling the intricate regulatory signals required for cornea and lens development has made it possible to harness the lineage growth potential of stem cells for cornea repair and lens regeneration, as showcased in two recent studies published in the March 17th issue of Nature.

We devoted this short piece to highlight one recent article published in Science, which revisited the anti-cancer efficacy of high-dose vitamin C. Using isogeneic KRAS- and BRAF-mutated colorectal cell lines, the authors were able to demonstrate selective anti-tumor effects among the KRAS- and BRAF-mutated cells in culture and in ex-planted animal models treated with high-dose vitamin C. Their elegant and in-depth studies unequivocally tied the tumoricidal effect to the heightened sensitivity of the mutant cells due to the increased vitamin C uptake, leading to lethal accumulation of reactive oxygen species (ROS). This report will certainly rekindle enthusiasm in revisiting the case of vitamin C, pushing for more definitive cancer therapy trials.

We devote this short piece to highlight one recent article published in Cell Stem Cell, reporting the correction of large chromosomal inversions of the factor Ⅷ (F8) gene in cells from Hemophilia A patients using the CRISPR-Cas9 technology, one of the first attempts to edit large segments of chromosomes in patient cells using such methodology. The corrected cells were found free of off-target mutations and producing functional factor Ⅷ in hemophilia mouse model. This work heralds another major advance in bringing CRISPR closer to the therapeutic reality.