Case Report: Allogeneic adipose-derived mesenchymal stem cells for severe feline chronic kidney disease

Abstract

A 10-year-old neutered male Ragdoll cat presented with symptoms of anorexia, nausea, vomiting, lethargy, and progressive weight loss. Laboratory parameters and clinical signs led to a diagnosis of International Renal Interest Society (IRIS) Chronic Kidney Disease (CKD) Stage III. Following basic supportive therapy, clinical symptoms subsided, and the patient was discharged for home management. Three months later, the cat's condition worsened, and upon reassessment, it met the diagnostic criteria for IRIS CKD Stage IV. After 4 months of guideline-directed supportive care (in accordance with IRIS recommendations), there were no significant changes in clinical symptoms or laboratory markers, and the cat continued to exhibit a cachectic condition. Subsequently, allogeneic adipose-derived mesenchymal stem cell (AD-MSCs) therapy (2 × 10⁶ cells/kg) was initiated via intravenous (IV) infusion, administered weekly for three consecutive weeks. No adverse events, such as fever or vomiting, were observed during or after therapy. Prior to AD-MSCs therapy, the cat's serum creatinine (SCr), blood urea nitrogen (BUN), and phosphorus (P) levels were all above the normal reference ranges. Three weeks after the final of the three AD-MSC treatments, the SCr level had returned to the reference range for CKD Stage II, while BUN and P levels showed an improving trend. The cat's mental status and appetite also improved. Reevaluation according to IRIS CKD staging criteria confirmed functional enhancement from Stage IV to Stage II. During the subsequent follow-up period, the cat's physical condition improved, as shown by an increase in body weight, an improved Body Condition Score (BCS), and the normalization of mucous membrane color. Concurrently, laboratory results revealed a decrease in key renal biomarkers (SCr, BUN, and P) and an amelioration of the non-regenerative anemia. This case report suggests that allogeneic AD-MSCs have potential therapeutic efficacy in felines with end-stage CKD, offering a new possibility for the treatment of terminal chronic kidney disease.

Keywords: adipose; chronic kidney disease; feline; mesenchymal stem cells; paracrine effects.

Figure 1

Renal ultrasound image. (A) Left renal length. (B) Right renal length.

Figure 2

Feline adipose tissue and characterization of AD-MSCs. (A) Feline adipose tissue. (B) ×50 magnification; (C) ×100 magnification; (D) ×200 magnification; feline AD-MSCs show a spindle-shaped morphology. (B–D) Scale bars, 100 μm. (E–I) The FCM analysis has shown that feline AD-MSCs highly expressed CD29, CD44, CD90, and CD105 but did not express CD34. (J) Adipogenic differentiation, evaluated using Oil Red O staining. (K) Osteogenic differentiation, evaluated using Alizarin Red staining. (L) Chondrogenic differentiation, evaluated using Alcian Blue staining. (J–L) Scale bars: 50 μm (J); 100 μm (K,L).

Figure 3

Serum creatinine, BUN, and phosphorus dynamics in a cat with chronic kidney disease during long-term conventional therapy and subsequent AD-MSCs treatment. (A) Serum creatinine (SCr) concentration over time (μmol/L). (B) Blood urea nitrogen (BUN) concentration over time (mmol/L). (C) Serum phosphorus (P) concentration over time (mmol/L). The yellow shaded area indicates the period of AD-MSCs treatment. The encircled numbers ①–⑤ on the figure represent measurements taken at the following time points: ① before the first injection (baseline); ② before the second injection; ③ before the third injection; ④ 1 week after the third injection; ⑤ 3 weeks after the third injection. Asterisks (*) indicate values that reached the upper limit of the instrument’s detection range. Day 0 was defined as the day treatment commenced upon the cat’s initial hospitalization in August 2023, serving as the baseline for the clinical timeline. a, b, and c indicate the time points of the first, second, and third mesenchymal stem cell infusions, respectively.