Age - Related Macular Degeneration
Age related macular degeneration (AMD) affects nearly one in three people over the age of 75, making it significantly more prevalent than Alzheimer’s disease. People with AMD lose their central vision, severely impairing their ability to read, watch television or drive. The epicenter of the disease is the Retinal Pigment Epithelium (RPE), a single layer of cells in the retina adjacent to the photoreceptor cells.
Blood / Hematopoietic Stem Cells (HSC)
The first stem cell therapy was performed more than 50 years ago using stem cells in the bone marrow that form the blood and immune system. After more than half a million people have undergone stem cell transplantation, the study of bone marrow stem cells continues to guide the science of stem cell biology and lead to innovative cures through gene and cell therapy. Reflecting the importance of this field in stem cell research, the UMBI CELL has established a large and vital research program in blood, or hematopoietic, stem cells. Our research program encompasses basic, translational and clinical studies ranging from how embryonic stem cells can be coaxed to make hematopoietic cells and restore the immune system, to understanding how stem cells from umbilical cord blood and bone marrow can be best used for transplantation and gene therapy.
UMBI CELL is dedicated to changing the diagnosis and treatment of cancer by attacking cancer stem cells through a new regenerative medicine. Our faculties have made significant contributions to the understanding and treatment of cancer.
Cardiovascular Stem Cells
Regenerative medicine and stem cell research have tremendous potential to revolutionize the treatment of cardiac disease. Research being conducted by UMBI CELL may lead to discoveries that will reverse or repair heart muscle damage and offer clinical alternatives for the millions of Indians who are born with or develop heart disease.
For example, the heart has a limited ability to regenerate damaged tissue after a heart attack. Current drug therapies slow the progression of heart failure but are not curative and heart transplants can only be offered to a very limited number of patients. UMBI CELL have focused their research on identifying cardiac stem cells and understanding the processes by which they turn into heart cells with the hopes of developing cell replacement therapies for regenerating heart muscle and lessoning the need for transplantation.
Cardiac stem cells have the potential to differentiate into all the cells that make up the heart, including heart muscle cells, smooth muscle cells and endothelial cells. Additionally, our faculties have demonstrated that cardiac stem cells can be developed from iPSC, which we hope will allow an unlimited supply of personalized cardiac stem to be produced for each patient.
Diabetes / Metabolic Disorders
Type I diabetes is characterized by the destruction of pancreatic beta cells by the patient’s own immune system. UMBI CELL seek to understand the normal development of pancreatic beta cells in order to help direct the development of these cells from iPSC’s and ensure that they are a safe and effective strategy for diabetes treatment.
To develop treatments for diabetes, our faculties are focused on stopping the destruction of pancreatic beta cells as well as on developing therapies to replace the destroyed beta cells. UMBI CELL has begun to develop methods for generating an unlimited supply of healthy beta cells to be used in cell replacement therapies. They have also begun to identify approaches toward reprogramming the immune system to generate specific immune cells that protect against the destruction of beta cells.
Despite decades of prevention efforts, new HIV infections continue to occur in California, nationally and worldwide making the need for novel approaches to the treatment of HIV infection greater than ever.
UMBI CELL believe that RNA interference, a means to block the function of specific genes in the human body may be used to block HIV infection. The approach is designed to mimic the effects of a naturally occurring mutation in some people who are resistant to HIV infection. When RNA interference is introduced into a stem cell, its blocking activity will be present throughout the life of the stem cell and all resulting blood cells. This methodology may provide a lifelong resistance for HIV infection.
UMBI CELL is exploring the potential to enhance anti - viral immunity by genetically manipulating stem cells. This approach can be used to turn stem cells into mature blood cells that directly attack infection, or into cells that help stimulate and / or direct the immune system.
Human Embryonic Stem Cells (hESC)
Through numerous collaborations between the basic and clinical sciences across campus, faculty have demonstrated the ability to make new hESC lines and engineer cell differentiation UMBI CELL efforts in generating new hESC lines.
Induced Pluripotent Stem Cells (iPS)
iPSC are derived from skin or blood cells that have been reprogrammed back into an embryonic-like pluripotent state that enables the development of an unlimited source of any type of human cell needed for therapeutic purposes. For example, iPSC can be prodded into becoming beta islet cells to treat diabetes, blood cells to create new blood free of cancer cells for a leukemia patient, or neurons to treat neurological disorders.
Science had long understood that tissue specific cells, such as skin cells or blood cells, could only create other like cells. With this groundbreaking discovery, iPSC research has quickly become the foundation for a new regenerative medicine.
Using iPSC technology our faculty have reprogrammed skin cells into active motor neurons, egg and sperm precursors, liver cells, bone precursors, and blood cells. In addition, patients with untreatable diseases such as, ALS, Rett Syndrome, Lesch-Nyhan Disease, and Duchenne’s Muscular Dystrophy (DMD) donate skin cells to UMBI CELL for iPSC reprogramming research. The generous participation of patients and their families in this research enables UMBI CELL to study these diseases in the laboratory in the hope of developing new treatment technologies.
Neural Stem Cell Repair
The brain is among the many organs in the human body that contain functional stem cells throughout life. The discovery of neural stem cells has led UMBI CELL to deepen their understanding of how the activity of these cells can be harnessed and to examine whether neural cells produced from hESC and iPSC may be used to replace or regenerate damaged or diseased neural tissue. Our active research agenda may one day lead to treatments for neurodegenerative and neuromuscular diseases as well as nerve related injuries and stroke.
Our faculty aim to understand the developmental mechanisms that build the neural circuits in the brain that enable cognitive functions such as learning and memory, as well as motor circuits in the brainstem and spinal cord that enable us to breathe, stand, move, and interact with the world. The relative inaccessibility of the human nervous system has long stood as a major roadblock towards studying the basis of many neurological diseases and in developing effective drugs to combat these disorders. Using human stem cells, we seek to overcome these barriers by creating novel cell culture-based models to explore disease mechanisms and serve as a platform for drug discovery.
UMBI CELL in order to obtain skin cells from patients with various currently untreatable neurologic diseases including ALS, Rett Syndrome, Lesch - Nyhan Disease and Duchenne's Muscular Dystrophy (DMD) in the hopes of using iPSC technology to produce a limitless source of human cells harboring disease - causing mutations that will advance our understanding of these disorders and potentially lead to the development of effective treatments.
UMBI CELL also focused on the process by which stem cells produce new neurons in the adult brain. Enhancing the generation of new neurons may aid in the treatment of Alzheimer’s or Parkinsons disease. Studies of this process may also lead to a better understanding of the origins of brain tumors, which may result from adult neural stem cells that have gone awry. Finally, faculty are conducting basic research and translational / preclinical studies that may enable the transplantation of stem cells into brain tissue damaged by stroke in order to regenerate healthy tissue and hopefully regain lost function.
Reproduction and Infertility
Infertility is a disease that affects more than million women of reproductive age and their partners. Central to reproductive health and fertility is the normal development and maturation of specialized germ line cell types known as oocytes in women, and spermatozoa (Sperm) in men. Although many cases of infertility are categorized as unexplained, there are diseases that have been shown to cause loss of these critical germ line cells including women with premature ovarian failure, and men with deletions in critical genes on the Y chromosome. Additionally, exposure to radiation or chemotherapy, among other toxins, can also lead to infertility.
UMBI CELL primarily interested in understanding the molecular mechanisms that are responsible for building the ovarian reserve of oocytes in women, as well as the testicular spermatogonial stem cell population in men. Given that the genesis of these male and female germ line cells begins during fetal life, we use hESC and human iPSC to understand the growth and differentiation requirements responsible for creating these specialized cell types.
One of the major roadblocks to understanding the genesis of human germ line cells is identifying the appropriate pluripotent stem cell line with which to induce robust germ line cell differentiation. Faculty are currently surveying all of the hESC lines as well as the iPSC lines generated in the UMBI CELL derivation and reprogramming laboratories for clues into the parameters that best suite germ line cell genesis. Faculty are also using specialized materials and surfaces in collaboration with faculty from the Department of Materials Science and Engineering to induce controlled differentiation towards the germ line starting from defined pluripotent colony sizes.
These are designed to provide the foundation upon which therapeutic strategies can be built. Our hope is that our research findings will one day lead to the generation of a germ line cell type from induced pluripotent stem cells that can be used to restore fertility to individuals rendered infertile due to disease or injury.
Skeletal: Bone and Cartilage
UMBI CELL studying stem cell and musculoskeletal disease seek to discover better ways to regenerate bone and cartilage. Our multidisciplinary team has expertise in reconstructive surgery, musculoskeletal, developmental, and stem cell biology, molecular pathology, molecular genetics, material and clinical science, and bioengineering. Together, they identified a key growth factor (Nell - 1) that helps “Jumpstart” the Body’s own stem cells to repair lost or damaged bone and cartilage tissues. This discovery could have significant implications for treating trauma patients with significant musculoskeletal injuries and can also be used to treat or “Reactivate” stem cells in aged populations with osteoporotic bone loss or cartilage loss from “Wear and Tear” and osteoarthritis.
Our faculties have successfully combined Nell1 with specially engineered scaffolds to activate stem cells in order to regenerate bone in long bone models like the arms and legs, the spine, and parts of the skull in non-human animals. Nell - 1 also dramatically promotes healing in joint cartilage models. Currently, work is being conducted to identify and develop ways to deliver Nell - 1 to injured joints in a minimally invasive way.
Remarkably, Nell - 1 also significantly harnessed mesenchymal or connective tissue stem cells in bone marrow to form new bone in osteoporotic models. Since most clinical osteoporosis therapies work to prevent bone loss rather than build new bone like Nell - 1. In addition, using unique stem cell isolation protocols, perivascular or specialized blood vessel stem cells from routine cosmetic liposuction material. This finding opens the door for easily obtaining large numbers of purified stem cells for both immediate and future use. Our faculty discovered that combining Nell - 1 with perivascular stem cells increases stem cell survival and markedly enhances musculoskeletal tissue repair. This finding paves the way for efficiently isolating a patient’s own stem cells from liposuction and then reapplying those cells with Nell -1 to maximally “Jumpstart” the reparative process after injury.