Stem Cell Biology & Therapy

(Professor Ariff Bongso, A/Prof Fong Chui Yee)

Our stem cell team has pioneered several world’s firsts in the field of stem cell biology. The team developed a novel coculture system to grow human embryos to 5-day blastocysts from which they isolated the world’s first embryonic stem cells (ESCs) in 1994. Thereafter, they developed several research-grade ESC lines, demonstrated the differentiation of ESCs into neuronal lineages and generated the first protocols for the derivation of clinical-grade ESC lines.

Their work was then extended to extra-embryonic membranes. They derived mesenchymal stem cells from the Wharton’s jelly (hWJSCs) of the human umbilical cord. These stem cells have several unusual stemness properties being primitive and protected from the insults of the external environment during pregnancy. They can be differentiated into desirable tissues, possess immunomodulatory and anticancer properties and have a unique secretome that contains a variety of useful molecules for tissue repair. Their engraftment, safety and regenerative ability have been demonstrated in recent FDA-approved human clinical trials.

The team’s preliminary work showed that hWJSCs and its conditioned medium inhibited the growth of lymphoma cells via immunogenic cell death and also supported the ex vivo expansion of hematopoietic stem cells (HSCs). Taken together, the team is evaluating the hematopoietic engraftment potential of HSCs co-transplanted with hWJSCs in preclinical xenograft animal models with the hope of providing alternate treatment strategies for malignant hematopoietic diseases,

The team showed in laboratory studies and murine models that a polycaprolactone (PCL) + aloe vera (AV) nanocarrier impregnated with hWJSCs or its conditioned medium served as a novel wound dressing patch for improved healing of surgical and diabetic wounds, and keloid suppression. They are currently evaluating these results in the diabetic pig model, attempting to identify the wound healing molecules in the hWJSC secretome and extending their work to human clinical trials for the treatment of diabetic foot ulcers. The team is also extending the evaluation of their patches for treatment of bed-sores in the elderly and for prolapse of the uterus. The team has filed several patents on the uses of hWJSCs including wound healing and keloid suppression. For downstream clinical applications, the team is developing cGMP-compliant hWJSC lines.

The infants of mothers with gestational diabetes mellitus (GDM) have an increased risk of metabolic and cardiovascular disease. It has been difficult to study the direct effects of maternal hyperglycemia on the fetus because of inaccessibility of fetal tissues. The development of tissues that mimic the function of fetal organs provides an unprecedented opportunity to study this disorder. The team produced tissues that physiologically and genetically simulate the infant of the diabetic mother by reprogramming fetal hWJSCs from normal and GDM umbilical cords into iPSCs and then differentiating them into pancreatic islet and cardiovascular cells to study the effects of hyperglycemia. The team is also evaluating the use of brain organoids derived from reprogrammed hWJSCs as a platform to study the pathogenesis and screening of antiviral drugs for the Zika virus and evaluation of agents that have potential teratogenic effects on the developing fetus.

Intrauterine transplantation of human and progenitor cells (HSPC) offers a novel approach to the treatment of the major thalassaemias prenatally. However, one of the main obstacles is the low engraftment of long-term repopulating HSPCs, insufficient to effect a clinical cure due to the physiological barriers within the haemopoietic niche. The team is evaluating in preclinical murine models of beta thalassaemia major, the use of donor HSPCs that may achieve long-term functional engraftment and erythropoietic correction when their haematological function is primed ex-vivo through coculture with hWJSCs prior to transplantation.