Cryopreservation of Embryonic Progenitors Derived from Human Embryonic Stem Cells
Efficient cryopreservation and banking of stem cells and stem cell-derived products is a critical component of any comprehensive plan for using these products to regenerate tissues in clinical settings. Banking stem cells and their derivatives provides sufficient time between derivation of cell products and their subsequent distribution to medical centers for safety and efficacy testing to be accomplished. Unfortunately, current methods for cryopreservation of human embryonic stem cells and derivative cell lines are inefficient, hampered by poor recovery, loss of “stem-ness” or self-renewal capability, and changes in gene expression that indicate the nature of the cells has altered during cell processing. Cryopreservation is stressful to cells because it causes rapid changes in water content, formation of dangerous ice crystals, exposure to chemicals that prevent ice crystals but are themselves somewhat toxic, and significant shifts in temperature. Improvements in cryopreservation protocols that minimize cell damage and maintain stem cell characteristics needed for their ability to relocate to and regenerate the corresponding tissues are direly needed. Such improvements will allow the development of an inventory of stem cell products relevant to the wide range of diseases for which stem cell therapy may be applicable. The proposed research will investigate the efficacy of varied cryopreservation protocols on stem cells and populations of stem cell derivatives that appear to represent unique tissues, including some with demonstrated ability to regenerate tissues and restore organ function. Two novel approaches to protect these cells against the stress of cryopreservation will be tested, including the use of a new generation of freezing solutions and a strategy that employs a naturally occurring cell survival signaling pathway known to protect cells against a variety of other biological stress conditions.
Efficient cryopreservation of stem cell products is a critical component of any comprehensive plan for implementing human tissue regeneration interventions. Improvements in cryopreservation will facilitate banking and safety/efficacy testing of stem cell products relevant to the wide range of diseases for which stem cell therapy may be applicable. The number of Californians who stand to benefit are indicated by yearly mortality rates for coronary heart disease (CHD, 52,000), diabetes-related problems (27,000) and stroke (16,000) and by nonfatal head and spinal cord injury hospitalization rates (25,000 and 1400 per year, respectively).
With respect to the tremendous ethnic and racial diversity of California, the impact will be felt across all communities. Hispanics have the highest rate of work-related injuries including burns and trauma. African Americans have the highest rates of CHD and stroke. Pacific Islanders have the highest rates of diabetes-related deaths, followed by African Americans and then Hispanics. Hemoglobinopathies such as sickle cell disease and thalassemia are primarily diseases of African Americans and persons of Asian, Mediterranean and Middle Eastern descent. Craniofacial malformations that affect 1 in 700 children overall have the highest incidence in Native Americans (1 in 300) and Hispanics (1 in 500).
Whereas men are by far more likely to suffer head and spinal cord injuries, approximately 12% of American women of childbearing age have sought help for infertility. Improved cryopreservation of gonadal stem cells and oocytes would be a significant benefit to women’s health.
As an example of the impact on California’s children, pediatrics burns affect 100, 000 children nationwide per year. The tremendous impact of childhood mortality or disability on society can be better appreciated by measuring years of life and productivity lost. Using this measure, cancer and heart disease still have the highest impact on years lost due to the large numbers of California adults affected by these diseases. However, unintentional injuries and congenital malformations were also ranked highly (3rd and 7th), due to the younger ages of the affected persons.
The financial burden of stem cell treatable illnesses is highly significant. For example, in California surgical costs to state service agencies average over $1.5 million per child affected by cleft lip or palate. However, the cost of hospitalizations and surgical treatments does not reflect the indirect toll. For adults, these include costs to industry due to the impact of absenteeism and lost productivity, costs to public programs accountable for their beneficiaries, and other costs to society.
In total, the impact of this research is far-reaching with respect to individual lives saved, range of medical conditions, racial and ethnic diversity, women’s health, the state’s economic health and the future generations who will contribute to and enjoy California’s long-term well-being.