Treatment effects of human amnion-derived mesenchymal stem cells for skin lesions and metastatic pulmonary calcification in calciphylaxis patients – case series and literature review

Calciphylaxis, also termed calcific uremic arteriolopathy (CUA) in patients with end-stage kidney disease (ESKD), is a rare and fatal condition characterized by cutaneous ischemic necrosis. Three patients with calciphylaxis and metastatic pulmonary calcification (MPC) were treated with human amnion-derived mesenchymal stem cells (hAMSCs). Effects were evaluated using the Visual Analogue Scale (VAS), modified Bates-Jensen Wound Assessment Tool for CUA (BWAT-CUA), wound quality of life questionnaire (Wound-QoL), and histological analysis. MPC was assessed by high-resolution CT (HRCT) and ⁹⁹ᵐTc-methylene diphosphonate (⁹⁹ᵐTc-MDP) bone scans.⁹⁹ᵐTc-labeled macroaggregated albumin (⁹⁹ᵐTc-MAA) pulmonary perfusion imaging was conducted for the first time in patients with MPC. Three patients exhibited wound healing and improvement in skin symptoms. Two months before CUA, asymptomatic MPC was detected in Patient 1, who was treated with hAMSCs for 15 months. The condition progressed to chest pain and dyspnea. HRCT and ⁹⁹ᵐTc-MDP bone scans showed worsening calcification, particularly in the upper and mid-thoracic lobes.⁹⁹ᵐTc-MAA pulmonary perfusion imaging revealed impaired or absent blood perfusion in the areas of metastatic calcification. Patient 1 died from respiratory failure. Patients 2 and 3 had asymptomatic MPC at calciphylaxis diagnosis. After 2 months of treatment, Patient 2, showed no significant imaging improvement and passed away 6 months after discontinuing hAMSC treatment. Patient 3 has shown no significant progression of pulmonary lesions and continues hAMSC therapy. We reported personalized early, noninvasive diagnosis and regenerative treatments for calciphylaxis patients with MPC. Although the current hAMSC treatment regimen is effective for skin lesions, its impact on MPC requires further investigation.

钙化防御（Calciphylaxis）又称尿毒症性钙化性小动脉病（CUA），是终末期肾病（ESKD）患者中发生的一种罕见且致命的疾病，以皮肤缺血性坏死为核心病理特征。本研究纳入3例合并转移性肺钙化（MPC）的钙化防御患者，予以人羊膜来源间充质干细胞（hAMSCs）治疗。采用视觉模拟评分法（VAS）、改良Bates-Jensen创面评估工具（BWAT-CUA）、创面生命质量问卷（Wound-QoL）及组织学分析对治疗效果进行评估；通过高分辨率CT（HRCT）与⁹⁹ᵐTc-亚甲基二膦酸盐（⁹⁹ᵐTc-MDP）骨显像评估转移性肺钙化情况。本研究首次将⁹⁹ᵐTc标记大颗粒聚合白蛋白（⁹⁹ᵐTc-MAA）肺灌注显像应用于转移性肺钙化患者的临床检测。

3例患者均出现创面愈合与皮肤症状改善。患者1在确诊钙化防御前2个月即被检出无症状性转移性肺钙化，随后接受了15个月的hAMSCs治疗，此后病情进展为胸痛与呼吸困难。高分辨率CT与⁹⁹ᵐTc-MDP骨显像显示钙化灶负荷加重，尤以中上肺叶为著。⁹⁹ᵐTc-MAA肺灌注显像显示转移性钙化区域的血流灌注受损或缺失。患者1最终因呼吸衰竭死亡。患者2与3在确诊钙化防御时即存在无症状性转移性肺钙化：接受治疗2个月后，患者2的影像学检查未显示显著改善，并在停用hAMSCs治疗后6个月死亡；患者3的肺部病变未见明显进展，目前仍在接受hAMSCs治疗。

本研究报道了针对合并转移性肺钙化的钙化防御患者的个体化早期无创诊断与再生治疗方案。尽管当前的hAMSCs治疗方案对皮肤病变具有一定疗效，但其对转移性肺钙化的干预效果仍需进一步深入研究。