by Angela C.H. McDonald
In 1988, the first umbilical cord hematopoietic stem cell transplant was conducted and since that time, over 20,000 umbilical cord blood transplants have been reported around the world. The technique offers several advantages over bone marrow in the treatment of blood disorders including noninvasive accessibility to umbilical cord blood as well as decreased graft versus host disease and superior immune recovery following transplantation.
Despite these advantages, umbilical cord blood transplantation remains best suited to small children due to the low cell numbers available in a single umbilical cord blood unit that make it of limited use in adult patients. Transplantation of two cord blood units has improved the outcome of adult patients, but there are simply not enough cords available to make this a viable strategy in the long term.
To overcome this hurdle, researchers have been looking for methods to culture cord blood in vitro with an aim to expand the numbers of stem cells found in a single cord unit and thus to circumvent the need to use two umbilical cord blood units for an adult patient.
It would seem we are getting close. Last month, a method for expanding human umbilical cord blood hematopoietic stem cells was published in Cell Stem Cell. Lead researcher Peter Zandstra and colleagues used computational and experimental approaches to design a strategy that yields an 11-fold increase of self-renewing, multi-lineage repopulating hematopoietic stem cells within 12 days of umbilical cord blood culture.
In culture, hematopoietic stem cells rapidly produce mature blood cell types that subsequently produce secreted factors inhibiting hematopoietic stem cell expansion. The trick is to dilute accumulating inhibitory factors to allow expansion of the stem cell pool. The researchers computationally simulated hematopoietic stem cell population dynamics and culture strategies and identified a culture system to do just that.
Simulations predicted that an input stream of fresh media into the culture would lead to an increase in total volume over time and would be the most effective strategy for expanding the stem and progenitor cell pools. This prediction was tested experimentally and proved to increase stem and progenitor cell number by reducing the concentration of accumulating inhibitory factors as well as maintaining lower cell densities in culture, effectively slowing the rate and impact of inhibitory factor accumulation.
This culture system – known as a fed-batch culture system – provides multiple advantages over other inhibitory factor dilution methods of umbilical cord cell expansion, including lower costs due to a decreased requirement for culture media as well as a shorter culture time window. The researchers hope to move this technology into clinical trials in the near future.
While significant steps forward in the optimization of cord blood transplantation for the treatment of blood disorders are being made, a number of researchers are exploring alternative therapeutic uses for cord blood stem cells. Earlier this year, a Phase I clinical trial was approved to treat hearing impairment in small children with their own cord blood stem cells.
In a mouse model of hearing loss, studies have demonstrated that cord blood can restore inner ear organization and structure two months following transplantation. How do cord blood stem cells treat hearing loss? Researchers aren’t quite sure. Cord blood stem cells may regenerate lost hair cells in the cochlea, restoring function or they may home to the site of injury in the ear and induce the body’s repair mechanisms (click here to read more). Research is underway to uncover the mechanism of cord blood-mediated hearing restoration. While this research is preliminary, results from animal studies are intriguing and I know I will be waiting to hear about this study’s progress.