MO133: Multidisciplinary Regenerative Treatment for Rescuing a Severe Calciphylaxis Patient with Human Amnion-Derived Mesenchymal Stem Cells
Authors: Wang Ningning , Qin Lianju , Liu Kang , Xing Changying , Ning Song , Lu Yan , Zhang Zhihong , Zhang Jing , Xiao Yujie , Ye Xiaoxue , Wang Xiuqin , Yuan Yanggang , Bian Anning , LV Xiaolin , Zhao Jing , Liu Cuiping , LI Fan , Su Zhonglan , Liang Ningxia , Liu Jiayin 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis, with high mortality and no proven therapy. Here, we reported multidisciplinary regenerative treatment for rescuing a severe uremic calciphylaxis patient with human amnion-derived mesenchymal stem cells (hAMSCs).

METHOD
A 34-year-old uremic woman presented progressive skin ischaemia, large areas of painful malodorous ulcers and mummified legs. The patient was diagnosed as calciphylaxis based on clinical manifestations, laboratory examinations and skin pathological features. Because of her refractory to conventional therapy, treatment with hAMSCs was approved. HAMSCs were administered intravenously to the patient at a dose of 1.0 × 106 cells per kilogram of body weight, local intramuscular injection along the wound edge (2.0 × 104 cells/cm2) and external application of the cell culture supernatant on wound surfaces.

RESULTS
Following up 15 months regularly after hAMSCs treatment, the patient's blood biochemical, inflammatory, mineral and bone metabolic indices improved significantly, with immunoregulation effects, regeneration of skin and soft tissue. Besides, wound healing (Figure 1), pain status and quality of life, evaluated by Pain Visual Analog Scale, Bates-Jensen Wound Assessment and the wound-quality of life questionnaire were also improved significantly (Figure 2).

CONCLUSION
This case represented the new method of hAMSC regeneration therapy for uremic calciphylaxis with safety and effectiveness, which deserved further investigation.
Before hAMSC treatment, the patient had irregular ulcers on the buttocks and lower extremities, some of which were crusted on the surface or had purulent fishy discharge. Skin and soft tissue necrosis can be seen at the ulcerated area of the buttocks, localized deep to the fascia, with purulent secretions on the surface and brown pigmentation of the skin at the edge of the ulcer (Figure 1A and B). Because of her worsening symptoms and signs refractory to conventional therapy, the patient was given intravenous and local intramuscular injections of hAMSCs, supplemented by application of hAMSC culture supernatant to the wound. After 4 months of treatment, the sacrococcygeal wound has reduced size and become shallow with less exudate, some new granulation tissue was visible. The infection was controlled with pain significantly reduced (Figure 1C). After 12 months, most of the sacrococcygeal wound had healed with only a few erosions (Figure1D). Fifteen months later, her skin scarring of the wound was healed without pain (Figure 1E).
The pain Visual Analogue Scale (Figure 2A) showed that the pain was unbearable before treatment (10 points) and disappeared after 15 months of hAMSC treatment (0 point). BWAT (Figure 2B) showed that all the 13 indexes got 5 points (worst) before hAMSC treatment, with a total score of 65 points. After 15 months of hAMSC treatment, each index got 1 point (best), and the total score was 13 points. The Wound-QoL questionnaire (Figure 2C) showed that the 17 items were quantified as 4 points (very serious) before treatment, with a total score of 68 points. After 15 months of hAMSC treatment, the score was 0 (none at all), and the total score was 0.