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HSV INFECTION OF STEM CELLS MAY CAUSE GVHD IN TRANSPLANT RECIPIENTS ,[object Object],[object Object]

Stem cell therapies are not without complications ,[object Object],[object Object],[object Object]

HAEM ,[object Object],[object Object],[object Object],[object Object],[object Object]

Stem cell differentiation into DC ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Does HSV reactivated from latency by the immunosuppressive therapy that precedes SCT cause/contribute GVHD in SCT recipients through its ability to regulate the differentiation of CD34+ cells?

Study Design ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

RESULTS ,[object Object],[object Object],[object Object],[object Object]

[object Object],[object Object],Group I – patient 1

Rash diagnosed as GVHD grade 3 Group I – patient 1

[object Object],[object Object],[object Object],Group I – patient 1

Group I – patient 1 Circulating cells

Baseline skin is Pol negative DERMIS EPI DERMIS

Lesional skin(D+33) has Pol+ keratinocytes, dermal cells and LC (80%)

Lesional skin(D+33) has Pol+ dermal, CD34+ and CD1a+ (LC) cells (66%)

[object Object],[object Object],[object Object],[object Object],Group I – patient 3

[object Object],[object Object],[object Object],Group I – patient 3

Group I – patient 3 ,[object Object],[object Object],Rash BSA CD34+/Pol+ CD34+/Ecad+ CD14+/Pol+ CD1a+/Pol+ D+3 None 3.2 2.5 41.3 ND D+19 (day 3 of rash) 30-40% 1.5 0.72 26.3 ND D+29 70-80% ND ND ND ND D+42 20-30% 0.52 0.24 1.2 ND D+51 30-40% 1.6 1.1 7.2 8.9 D+63 10-20% 0.04 0.13 7.1 0.14

Pol expression increases with lesion severity Pol expression in epidermis/dermis correlates with clinical, not GVHD severity Epidermis Dermis Day 3 0 0 Day 19 (30-40% BSA) GVHD grade 2 19.6 ± 4 9.1 ± 1.1 Day 29 (70-80% BSA) 63.6 ± 5.1 49.6 ± 4.6 Day 51 (20-30% BSA) GVHD grade 3 22.8 ± 2.6 11.3 ± 2.8

Pol is expressed in lesional skin Baseline Day 29 Epidermis Dermis

CD34+ cells and their differentiation products target Pol to lesional skin CD34+/Pol+ CD14+/Pol+ CD1a+/Pol+ (71%) Dermis

[object Object],[object Object],[object Object],[object Object],Group II – patient 4

[object Object],[object Object],CONCLUSION

[object Object],[object Object],[object Object],[object Object],CONCLUSION

CONCLUSION ,[object Object],[object Object],The studies were supported by the Maryland Stem Cell Research Fund

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