J Korean Med Sci.  2020 Apr;35(15):e130. 10.3346/jkms.2020.35.e130.

Therapeutic Effects of Mesenchymal Stem Cells on a Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Model

• Park SY
• Oh IY
• Kim JH
• Kim HJ
• Seo B
• Kwon OY
• Song WJ
• Kwon HS
• Cho YS
• Moon HB
• Kim TB

• KMID: 2500193
• DOI: http://doi.org/10.3346/jkms.2020.35.e130

Abstract

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are the most severe cutaneous drug hypersensitivity reactions, which are unpredictable adverse drug reactions. SJS/TEN is associated with significant mortality and morbidity; however, effective treatment is difficult. Mesenchymal stem cells (MSCs) are well-known for their anti-inflammatory and tissue regeneration properties. The purpose of the present study was to verify whether MSCs could be applied for the treatment of SJS/TEN. We developed an SJS/TEN mouse model using peripheral blood mononuclear cells from a lamotrigine-induced SJS patient. MSCs were injected into the model to verify the treatment effect. In SJS model mice treated with MSCs, ocular damage rarely occurred, and apoptosis rate was significantly lower. We demonstrated a therapeutic effect of MSCs on SJS/TEN, with these cells presenting a potential novel therapy for the management of this disorder.

Keyword

Stevens-Johnson Syndrome; Toxic Epidermal Necrolysis; Mesenchymal Stem Cells; Drug Hypersensitivity; Adverse Drug Reaction

Figure

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  Fig. 1 Summary of the experimental design and schedules. A lamotrigine-induced SJS mouse model was constructed using PBMCs from one patient and the culprit drug, lamotrigine. Effects of MSCs were compared by dividing groups into whether or not MSCs were injected.SJS = Stevens-Johnson syndrome, PBMCs = peripheral blood mononuclear cells, MSCs = mesenchymal stem cells.

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  Fig. 2 MSCs reduce mucosal damage in a lamotrigine-induced SJS/TEN mouse model. (A) Ocular findings were obtained using an operating microscope. The corneal opacity grade is increased in group 5. (B) Hematoxylin and eosin staining. The shape of the limbus is distorted in group 5; however, mice receiving MSCs (group 4) show a normal limbus. (C) PAS staining. The proportion of PAS-positive cells (dark purple color) observed in group 4 is shown. (D) Terminal deoxynucleotidyl transferase dUTP nick end labeling. (E) Immunohistochemical granzyme B staining. The entire inner side of the cornea is stained positively (dark brown) for granzyme B. Group 1: untreated control; Group 2: PBMCs-only; Group 3: lamotrigine-only; Group 4: Model mice (PBMCs + lamotrigine) treated with MSCs; Group 5: Model mice (PBMCs + lamotrigine) without MSC treatment.PBMCs = peripheral blood mononuclear cells, MSCs = mesenchymal stem cells, SJS/TEN = Stevens-Johnson syndrome and toxic epidermal necrolysis, PAS = Periodic acid-Schiff.

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