Stem cell mobilization with plerixafor and healing of diabetic ischemic wounds: A phase IIa, randomized, double‐blind, placebo‐controlled trial

@article{Bonora2020StemCM,
  title={Stem cell mobilization with plerixafor and healing of diabetic ischemic wounds: A phase IIa, randomized, double‐blind, placebo‐controlled trial},
  author={Benedetta Maria Bonora and Roberta Cappellari and Marta Mazzucato and Mauro Rigato and Marco Grasso and Mirko Menegolo and Andrea Bruttocao and Angelo Avogaro and Gian Paolo Fadini},
  journal={Stem Cells Translational Medicine},
  year={2020},
  volume={9},
  pages={965 - 973}
}
Abstract Bone marrow‐derived cells contribute to tissue repair, but traffic of hematopoietic stem/progenitor cells (HSPCs) is impaired in diabetes. We therefore tested whether HSPC mobilization with the CXCR4 antagonist plerixafor improved healing of ischemic diabetic wounds. This was a pilot, phase IIa, double‐blind, randomized, placebo‐controlled trial (NCT02790957). Patients with diabetes with ischemic wounds were randomized to receive a single subcutaneous injection of plerixafor or saline… 
6 Citations

Tables from this paper

Hematopoietic and non-hematopoietic p66Shc differentially regulates stem cell traffic and vascular response to ischemia in diabetes.

Hematopoietic deletion of p66Shc was sufficient to rescue HSPC mobilization and homing in diabetes after ischemia and improved blood flow recovery, and inhibiting p66 Shc in blood cells may be a novel strategy to counter PAD in diabetes.

Cell Therapy for Critical Limb Ischemia: Advantages, Limitations, and New Perspectives for Treatment of Patients with Critical Diabetic Vasculopathy

The present review aims to provide an update of the ongoing work in the field of regenerative medicine on the perturbation of non-coding RNA networks in progenitor cells and the possibility of using emerging knowledge on molecular mechanisms to design refined protocols for personalized therapy.

(Accepted/In press). Cell Therapy for Critical Limb Ischemia: Advantages, Limitations, and New Perspectives for Treatment of Patients with Critical Diabetic Vasculopathy. Current diabetes reports.

The present review aims to provide an update of the ongoing work in the field of regenerative medicine on the perturbation of non-coding RNA networks in progenitor cells and the possibility of using emerging knowledge on molecular mechanisms to design refined protocols for personalized therapy.

Impaired Hematopoietic Stem/Progenitor Cell Traffic and Multi-organ Damage in Diabetes

The current evidence that diabetes affects HSPC traffic is summarized, which are the causes and consequences of such alteration, and how it contributes to the overall disease burden.

References

SHOWING 1-10 OF 46 REFERENCES

Autologous Cell Therapy for Peripheral Arterial Disease: Systematic Review and Meta-Analysis of Randomized, Nonrandomized, and Noncontrolled Studies.

A meta-analysis of studies evaluating safety and efficacy of autologous cell therapy for intractable peripheral arterial disease/critical limb ischemia showed that cell therapy reduced the risk of amputation, improved amputation-free survival, and improved wound healing by 59%, without affecting mortality.

Diabetes Limits Stem Cell Mobilization Following G-CSF but Not Plerixafor

Testing whether the CXCR4 antagonist plerixafor, differently from G-CSF, is effective in mobilizing hematopoietic stem cell (HSC) mobilization in patients with diabetes found it was equally able to mobilize CD34+ HSCs in the two groups, whereas in historical data, G- CSF was less effective in Patients with diabetes.

Decreased Circulating Progenitor Cell Number and Failed Mechanisms of Stromal Cell-Derived Factor-1α Mediated Bone Marrow Mobilization Impair Diabetic Tissue Repair

Plerixafor represents a potential therapeutic agent for improving ischemia-mediated pathology associated with diabetes by reducing bone marrow SDF-1α, restoring normal PC mobilization and tissue healing.

Global Remodeling of the Vascular Stem Cell Niche in Bone Marrow of Diabetic Patients: Implication of the microRNA-155/FOXO3a Signaling Pathway

New anatomic and molecular evidence is provided for the damaging effect of diabetes mellitus on human BM, comprising microvascular rarefaction and shortage of PCs attributable to activation of proapoptotic pathway.

CXCR4 Antagonist AMD3100 Accelerates Impaired Wound Healing in Diabetic Mice

A single topical application of AMD3100 promoted wound healing in diabetic mice by increasing cytokine production, mobilizing bone-marrow EPCs, and enhancing the activity of fibroblasts and monocytes/macrophages, thereby increasing both angiogenesis and vasculogenesis.

Defective recruitment, survival and proliferation of bone marrow-derived progenitor cells at sites of delayed diabetic wound healing in mice

Local treatments aimed at restoring EPC homing and survival might improve tissue healing in diabetes, as diabetic-delayed wound healing was associated with defective recruitment, survival and proliferation of BM-derived progenitor cells.

Granulocyte-colony stimulating factors as adjunctive therapy for diabetic foot infections.

It is suggested that adjunctive G-CSF treatment in people with a diabetic foot infection, including infected ulcers, does not appear to increase the likelihood of resolution of infection or healing of the foot ulcer, however, it does appear to reduce the need for surgical interventions, especially amputations, and the duration of hospitalisation.

Diabetes Impairs Hematopoietic Stem Cell Mobilization by Altering Niche Function

The authors suggest that AMD3100 could be used to boost HSC mobilization in diabetic patients who require a bone marrow transplant and suggest that HSPCs were aberrantly localized in the marrow niche of the diabetic mice, and abnormalities in the number of sympathetic nerve termini were associated with this mislocalization.

Diabetes Impairs Stem Cell and Proangiogenic Cell Mobilization in Humans

Stem and proangiogenic cell mobilization in response to hrG-CSF is impaired in DM, possibly because of maladaptive CD26/DPP-4 regulation.