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Preventing Transplant Rejection with Endometrial Regenerative Cell-Therapy and SDF-1

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Review of “Stromal Cell-Derived Factor-1 Mediates Cardiac Allograft Tolerance Induced by Human Endometrial Regenerative Cell-Based Therapy” from STEM CELLS Translational Medicine by Stuart P. Atkinson

While the long-term success of organ transplantation currently still depends on the delicate balance between under- and over-immunosuppression [1, 2], research teams across the globe still hope to encounter a more efficient strategy. Several studies have harnessed the immunomodulatory powers of mesenchymal stromal cells (MSCs); however, the optimal source for MSCs remains an unanswered, yet heavily studied, question. 

The research team of Hao Wang (Tianjin Medical University General Hospital, PR China) believes that endometrial regenerative cells (ERCs), mesenchymal-like stromal cells non-invasively obtained from menstrual blood, may be the answer, given their ease of collection, abundance, and MSC-like characteristics. Their recent study established that ERCs prolonged survival time of cardiac allografts via the suppression of B cell function in cardiac graft transplantation [3]. Now, their new STEM CELLS Translational Medicine study establishes how ERCs inhibit transplant rejection and induce allograft tolerance via the expression of Stromal cell-derived factor-1 (SDF-1) [4].

Lan et al. assessed the donation of cardiac grafts from a BALB/c mouse donor to a C57BL/6 recipient; a model expected to present with problems related to immune incompatibility. However, the intravenous co-delivery of in vitro amplified human ERCs alongside the immunosuppressant drug rapamycin induced donor-specific allograft tolerance, although coinjection of an SDF-1 receptor antagonist inhibited blocked this activity. Moreover, blocking SDF1 function also led to an increase in intragraft antibodies and infiltrating immune cells and a reduction in regulatory immune cell levels. 

Previous studies indicated that stem cell homing to injured tissues and organs requires SDF-1 [5] and so, the authors propose that SDF-1 expression enhances the migration of ERCs to the allograft in a protective role and also to the lymphoid organs where they promote immune tolerance.

Together, these data suggest that human ERC treatment could represent an exciting new means to prevent transplant rejection; stay tuned to the Stem Cells Portal to find out more about this approach!

References

  1. Lund LH, Edwards LB, Kucheryavaya AY, et al., The Registry of the International Society for Heart and Lung Transplantation: Thirty-second Official Adult Heart Transplantation Report--2015; Focus Theme: Early Graft Failure. J Heart Lung Transplant 2015;34:1244-54.
  2. Soderlund C and Radegran G, Immunosuppressive therapies after heart transplantation--The balance between under- and over-immunosuppression. Transplant Rev (Orlando) 2015;29:181-9.
  3. Xu X, Li X, Gu X, et al., Prolongation of Cardiac Allograft Survival by Endometrial Regenerative Cells: Focusing on B-Cell Responses. STEM CELLS Translational Medicine 2017;6:778-787.
  4. Lan X, Wang G, Xu X, et al., Stromal Cell-Derived Factor-1 Mediates Cardiac Allograft Tolerance Induced by Human Endometrial Regenerative Cell-Based Therapy. STEM CELLS Translational Medicine 2017;6:1997-2008.
  5. Petit I, Jin D, and Rafii S, The SDF-1-CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis. Trends Immunol 2007;28:299-307.