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Project details

Short lay summary

Various studies suggest that stem cells transplanted from a tissue-matched donor could provide benefits to patients with RDEB.  However, there are still many challenges, not only in developing stem-cell technologies, but also in identifying the best source of stem cells for maximum therapeutic effect.  This research group has previously shown that umbilical cord blood is an alternative source of stem cells for patients with no matched family donors, in both malignant and non-malignant conditions. The big disadvantage of cord blood compared with bone marrow is the delay in restoring a functioning immune system to the patient following cell transplantation, but these researchers showed that addition of other types of stem cells could overcome this problem.  This project investigated the regenerative functions of these cells cells and determined safety and feasibility of using these new stem-cell sources, as a prelude to a pilot clinical trial.

Scientific summary

The goal is to develop stem cell products as universal donor cell therapy and/or for third party facilitator therapy with related or unrelated cord blood (CB) hematopoietic progenitor cell (HPC) transplantation in selected patients with RDEB. In this study, the effects of human placenta derived stem cells (HPDSC),  already in clinical trial, were investigated in the treatment of RDEB. Furthermore, their previous DEBRA-funded studies in an RDEB mouse model also showed that another source of cord blood-derived stem cells, unrestricted somatic stem cells (USSCs), improved wound healing and significantly increased the life span of RDEB mice. This group further demonstrated that CB-derived USSCs suppress fibrosis and expression of genes correlated with chronic wound and malignant transformation in RDEB mice and RDEB patients-derived cells. Administration of HPDSCs and USSCs respectively, led to deposition of C7 at the dermal-epidermal junction and partial rescue of anchoring fibrils in the recipient RDEB mice.

Strategic relevance

  • DEBRA strategic goal: ‘Develop disease-modifying and curative therapies’ through research and clinical studies, to develop therapies that target the underlying disease mechanism in EB.
  • Project goal: to investigate clinical applicability of novel sources of stem cells for RDEB treatment.
  • Preceding/ follow-on projects, and related projects: This project builds on previous DEBRA funded projects  Cairo 1 (Umbilical Cord Blood Multi-lineage Stem Cells In The Treatment Of Recessive Dystrophic Epidermolysis Bullosa), and Cairo 2 (Therapeutic Potential of Human Umbilical Cord Blood-Derived Stem Cells in RDEB Animal Models)

What did this project achieve?

Stem cell research in mice that do not express type VII collagen (C7)  - an animal model of RDEB  - revealed two novel stem cell sources that may be valuable for treating RDEB: human placenta derived stem cells (HPDSCs) and human cord blood derived unrestricted somatic stem cells (USSCs).

The research showed that injection of HPDSC in newborn RDEB mice significantly increased the lifespan of the recipient mice and alleviated blistering. 

USSCs promote wound healing and improve blistering in the RDEB mice by migrating to wound sites, depositing C7 and by modifying the immune response. The research showed that USSCs downregulate genes related to fibrosis and upregulated genes that are anti-inflammatory. 

Neither USSC nor HPDSC resulted in significant immune responses to the C7 in the mice, suggesting the cells may be administered safely in the patients with RDEB as universal donors cells, as a stand-alone therapy, or together with allogeneic stem cell transplantation.


Keywords

RDEB
Wound healing
Fibrosis
Stem cells
Human placenta derived stem cells (HPDSCs)
Human cord blood derived unrestricted somatic stem cells (USSCs)
Cell therapy
Cairo
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