Atlanta, GA—The promise of regenerative medicine is exemplified by the regeneration of corneal epithelium from human limbal stem-cell culture.
The fields of regenerative medicine and hematology are relevant to one another, said Armand Keating, MD, Chair in Cell Therapy and Transplantation Director, Division of Hematology, University of Toronto, Canada and President of the American Society of Hematology (ASH) during the ASH 2012 Presidential Symposium, which focused on advances in regenerative medicine.
“The generation of hematopoietic stem cells from pluripotent stem-cells depends on our ability to accurately recapitulate key aspects of embryonic hematopoietic development in the differentiation cultures,” said Dr Keating. Stem-cell biology has been crucial to many of the clinical trials of regenerative medicine.
Gordon Keller, PhD, Director/Senior Scientist at the McEwen Centre for Reproductive Medicine in Toronto, Ontario, Canada, reviewed the progress in modeling human hematopoietic development from pluripotent stem cells (PSCs) in vitro. His laboratory has been involved in approaches to distinguish primitive and definitive hematopoiesis and in identifying the signaling pathways that regulate these processes.
Dr Keller described the identification of a PSC-derived definitive hematopoietic progenitor that develops from hemogenic endothelium and that displays the capacity to generate lymphoid, myeloid, and erythroid progeny.
Viewing the stem cell through the microenvironment, or niche, in which it resides has been the work of David Scadden, MD, Co-chair of the Department of Stem Cell and Regenerative Biology, and Co-director of the Harvard Stem Cell Institute, Boston, and his team. The key elements of the stem-cell niche in the bone marrow have been identified. Hematopoietic stem cells rely on complex cues from the bone marrow environment for their regulated activity, said Dr Scadden.
Using genetics, imaging, and pharmacology, Dr Scadden’s laboratory has demonstrated the methods of modifying niche interactions, prompting 2 clinical trials in the use of stem cells to treat hematologic malignancies.
Lessons from the Limbus
Basic research on corneal stem cells dates to the early 1990s. Michele De Luca, MD, Professor of Biochemistry and Director of the Centre for Regenerative Medicine and the Department of Stem Cells, University of Modena, and Reggio Emilia, Modena, and Graziella Pellegrini, PhD, Associate Professor of Cell Biology, Centre for Regenerative Medicine, University of Modena, Italy, were the first researchers to discover that cultured limbal cells include stem cells that are detectable as colonies, or holoclones. Holoclone-forming cells are the stem cells of virtually all human squamous epithelia, and thus are responsible for the renewal and repair of human stratified epithelium.
Self-renewal, proliferation, and differentiation of limbal stem cells are regulated by known transcription factors. Ocular burns can destroy the limbus, causing limbal stem-cell deficiency. In such cases, the cornea acquires an epithelium through the invasion of bulbar conjunctival cells, which causes neovascularization, chronic inflammation, and scarring that lead to the opacification of the cornea and vision loss.
The only way to prevent the invasion of conjunctival cells is to restore the limbus, said Dr De Luca. He reported the long-term results of a study in which cultured limbal stem-cell grafts were used for corneal transplantation in patients with burn-induced corneal damage.
Follow-up of up to 10 years showed that cultured limbal stem-cell grafts for corneal transplantation were successful in restoring the corneal epithelium and visual acuity in more than 75% of the patients.
