Impact of allogeneic feline uterine-derived mesenchymal stromal cell intravenous treatment on renal function of nephrectomized cats with chronic kidney disease

Zacharias, Shelly; Welty, M.; Sand, Theodore T.; Black, L.

doi:10.1016/j.rvsc.2021.09.015

Cited by 4 publications

(2 citation statements)

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“…These mesenchymal stem cells are derived from many different tissues and organs, such as dental pulp [ 32 ], amniotic fluid [ 33 ], umbilical cord [ 34 ], and bone marrow [ 35 , 36 ]. Our studies on uterine stem cells are further supported by a recent study showing that uterine-derived feline mesenchymal stem cells (UMSCs) have a therapeutic effect on chronic kidney disease (CKD) in cats [ 37 ]. Uterine-derived stem cells may be beneficial in the acute or chronic disease state.…”

Section: Discussionsupporting

confidence: 60%

Therapeutic role of uterine-derived stem cells in acute kidney injury

et al. 2022

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Background Acute kidney injury (AKI) causes abrupt deterioration in kidney function that disrupts metabolic, electrolyte and fluid homeostasis. Although the prevalence of AKI is steadily increasing, no definitive treatment options are available, leading to severe morbidity and mortality. We evaluated the role of uterine-derived multipotent stem cells in kidney regeneration after ischemic AKI. Methods Female C57BL/6J mice were hysterectomized and subsequently subject to AKI by either unilateral or bilateral renal ischemia–reperfusion injury. Uterine-derived cells (UDCs), containing a population of uterine stem cells, were isolated from the uteri of female transgenic DsRed mice and injected intravenously to AKI mice. Engraftment of DsRed cells was analyzed by flow cytometry while serum creatinine levels were determined colorimetrically. Expression of UDC markers and cytokine markers were analyzed by immunohistochemical and qRT-PCR methods, respectively. The Kaplan–Meier method was used to analyze survival time while unpaired t test with Welch’s correction used for data analysis between two groups. Results Mice with an intact uterus, and hence an endogenous source of UDCs, had a higher survival rate after bilateral ischemic AKI compared to hysterectomized mice. Mice treated with infusion of exogenous UDCs after hysterectomy/AKI had lower serum creatinine levels and higher survival rates compared to controls that did not receive UDCs. Engraftment of labeled UDCs was significantly higher in kidneys of bilateral ischemic AKI mice compared to those that underwent a sham surgery. When unilateral ischemic AKI was induced, higher numbers of UDCs were found in the injured than non-injured kidney. Immunofluorescence staining demonstrated double-positive DsRed/Lotus tetragonolobus agglutinin (LTA) positive cells and DsRed/CD31 positive cells indicating contribution of UDCs in renal tubular and vascular regeneration. Expression of Cxcl12, Bmp2, Bmp4, and Ctnf in renal tissue was significantly higher in the UDCs injection group than the control group. Conclusions UDCs engrafted injured kidneys, contributed to proximal tubule and vascular regeneration, improved kidney function and increased survival in AKI mice. UDC administration is a promising new therapy for AKI. Endogenous uterine stem cells likely also preserve kidney function, suggesting a novel interaction between the uterus and kidney. We suggest that hysterectomy may have a detrimental effect on response to renal injury.

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Section: Discussionsupporting

confidence: 60%

Therapeutic role of uterine-derived stem cells in acute kidney injury

et al. 2022

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“…All cAD studies to date have evaluated adipose-derived MSCs, requiring donors to undergo surgical excision of fat under general anesthesia (12)(13)(14)(15)(16). In contrast, uterine tissuederived MSCs (UMSCs) can be harvested from tissues removed during routine sterilization procedures, offering a virtually unlimited source of cells without additional surgery (17). Based on three in vitro studies, UMSCs have therapeutically favorable characteristics, with similar properties to adipose-derived MSCs, including proliferation in cell culture and high capacity for differentiation (18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

The effect of uterine-derived mesenchymal stromal cells for the treatment of canine atopic dermatitis: A pilot study

Black¹,

Zacharias²,

Hughes³

et al. 2022

Front. Vet. Sci.

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Canine atopic dermatitis (cAD) is a common allergic skin condition among dogs that may respond to treatment with mesenchymal stromal cells (MSCs). The aim of this pilot study was to evaluate the safety and efficacy of allogeneic uterine tissue-derived MSCs (UMSCs) for the reduction and control of clinical signs associated with cAD. At two sites, seven client-owned dogs with cAD received two doses of approximately 3.6 x 107 UMSCs given intravenously over 30 min, on Day 0 and Day 14, with monthly clinical follow-up until Day 90 and optional owner phone interview on Day 180. Primary outcomes were pruritus and skin lesions. Pruritus was measured by the owner-assessed Pruritus Visual Analog Scale (PVAS), with treatment success defined as a 2-point reduction in PVAS score at any timepoint after treatment. Skin lesions were evaluated by two veterinarians according to the Canine Atopic Dermatitis Extent and Severity Index (CADESI-4). The secondary outcome was safety, which was evaluated via physical exam and hematology, including complete blood count (CBC), serum chemistry, and urinalysis (UA). Treatment was generally well tolerated and associated with a significant reduction in PVAS on Day 30 that was maintained through Day 180. On Day 60, five dogs (71%) achieved treatment success (at least 2-point reduction in PVAS), and three dogs (43%) had a PVAS improvement of 4-5 points. Mean CADESI-4 score was significantly improved on Day 14, Day 30, Day 60, and Day 90, with the lowest mean score observed on Day 60. Three dogs exhibited mild and transient adverse events. These findings suggest that IV-administered allogeneic UMSCs reduce and control clinical signs of cAD, with a durable benefit lasting 3–6 months.

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