Horizontal Alveolar Ridge Splitting and Expansion.

INTRODUCTION

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by damaged and dysregulated immune system due to breakdown in the selection process during clonal growth of immune cells. Studies have shown that patients with systemic lupus erythematosus (SLE) display altered gene expression patterns and increased double-stranded DNA breaks within their hematopoietic stem and progenitor cells (HSPC). However, the current animal models for SLE found in the existing literature predominantly emphasize the use of peripheral blood mononuclear cells (PBMC) over HSPC for the creation of humanized mouse models. Nevertheless, these prior models were constrained by the limited efficiency of human cell engraftment and limited PBMC ability to replicate the capacity of HSPC to generate human SLE cells that can engraft host mice, thus making the transplant protocol inadequate.

PATIENTS AND

METHODS

Transplantation was initiated by extracting HSPC from stable SLE patients by leukapheresis. The collected cells were assessed for purity before storage at -80 °C. Humanized mice were conditioned with cyclophosphamide and total-body irradiation before receiving the HSPC transplant. After transplantation, the mice were administered human granulocyte-colony stimulating factor and sacrificed to evaluate autoantibodies and HSPC in their bone marrow and blood samples. Statistical analysis was performed using Student's t-test and one-way ANOVA.

RESULTS

Upon human stem cells engravement into mice, we found a noteworthy presence of HSPC, as evidenced by the positive expression of hCD45, hCD34, and/or hCD44, and the production of human antinuclear antibodies. The results indicated that the transplanted mice generated reactive autoantibodies against human cells, similar to that observed in the human donor patient. These findings shed light on the survival and behavior of transplanted human stem cells in a mouse model.

CONCLUSION

In this study, we successfully induced immunodeficiency in mice for xenotransplantation with human peripheral stem cells.