Placenta-Derived Decidua Stromal Cells for Hemorrhagic Cystitis after Stem Cell Transplantation

Severe acute graft‐versus‐host disease (GVHD) is a life‐threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). The placenta protects the fetus from the mother's immune system. We evaluated placenta‐derived decidua stromal cells (DSCs), which differ from bone marrow mesenchymal stromal cells (BM‐MSCs), as a treatment for severe acute GVHD. DSCs were obtained from term placentas. The DSCs were given to 38 patients with severe acute GVHD; 25 were steroid refractory (SR). DSCs were thawed and infused in buffer supplemented with either 10% AB plasma (group 1, n = 17), or 5% albumin (group 2, n = 21). The viability of cells was higher when thawed in albumin rather than AB plasma (p < .001). Group 1 received a higher cell dose (p < .001), cells of lower passage number (p < .001), and fewer infusions (p = .002) than group 2. The GVHD response (no/partial/complete) was 7/5/5 in group 1 and 0/10/11 in group 2 (p = .01). One‐year survival in the two groups was 47% (95% confidence interval [CI] 23–68) and 76% (95% CI 51–89), respectively (p = .016). For the SR patients, 1‐year survival was 73% (95% CI 37–90) in SR group 2 (n = 11), which was better than 31% (95% CI 11–54) in SR group 1 (n = 13; p = .02), 20% (95% CI 5–42) in BM‐MSC treated (n = 15; p = .0015), and 3% (95% CI 0–14) in historic controls (n = 32; p < .001). DSCs are a promising new treatment for severe acute GVHD. Prospective randomized trials are needed for evaluation of efficacy. (Clinical trial NCT‐02172937.) stem cells translational medicine 2018;7:325–332

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“…We also used DSCs successfully to treat acute respiratory distress syndrome and hemorrhagic cystitis .…”

Section: Resultsmentioning

confidence: 99%

Placenta-Derived Decidua Stromal Cells for Treatment of Severe Acute Graft-Versus-Host Disease

Ringdén¹,

Baygan²,

Remberger

et al. 2018

Stem Cells Translational Medicine

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“…Before treating patients, we injected DSCs to rats, as reported in this article and in rabbits (32) and found it to be safe with no side effects. Subsequently, we treated patients with acute and chronic GvHD, hemorrhagic cystitis and acute respiratory distress syndrome (30, 33, 41, 42). Side effects were minimal and severe adverse events were those commonly seen in patients undergoing allogeneic HSCT, such as infections, hemorrhages, graft failure and multi-organ failure (29, 33).…”

Section: Discussionmentioning

confidence: 99%

“…We previously reported on the good safety and efficacy of DSCs in treatment of GvHD and HC following HSCT (29, 30) as well as in experimental setting (31, 32). When employed at the typical low clinical cell doses, DSCs demonstrated a safe toxicity profile and no side effects in the clinical setting (33) and in an animal model of BMT and GvHD (31).…”

Section: Introductionmentioning

confidence: 99%

Preclinical Toxicity Evaluation of Clinical Grade Placenta-Derived Decidua Stromal Cells

et al. 2019

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Placenta-derived decidua stromal cells (DSCs) are being investigated as an alternative to other sources of mesenchymal stromal cells (MSCs) for cellular therapy. DSCs are more effective in treating acute inflammatory diseases in human and this is our preclinical safety study of human DSCs in Sprague-Dawley rats and Balb/c mice. Human DSCs were cultured and expanded from fetal membranes obtained from placentas following cesarean section. In rats, 0.5 × 106 cells/kg were injected intravenously (n = 4) or intra-aortal (n = 4). In mice, DSCs were given intravenously at doses ranging from 4–40 × 106 cells/kg (total of n = 120 mice). In vivo tracking of human cells in mice was performed by using transduced DSC with luciferin gene, and in rats by using 18F-FDG PET. Clotting parameters were determined in vitro and in vivo. All intra-arterially DSC-treated rats had normal motility and behavior and histological examination was normal for liver, spleen kidneys and thigh muscles. Mice treated with DSCs showed no immediate or long-term side effects. None of the mice died or showed acute toxicity or adverse reactions 3 and 30 days after DSC infusion. Murine blood biochemistry profiles related to liver, kidney, heart, and inflammatory indices was not influenced by DSC infusion and complete blood counts were normal. In vivo tracking of infused DSCs detected a signal in the lungs for up to 4 days post infusion. Compared to bone marrow derived MSCs, the DSCs had better viability, smaller size, but stronger clotting in human blood and plasma. Both MSC- and DSC-induced coagulation and complement activation markers, thrombin-anti-thrombin complex (TAT) and C3a, and in vitro clotting parameters were decreased by heparin supplementation. In conclusion, DSCs are safe with almost no side effects even with doses 40 times higher than are used clinically, particularly when supplemented with low-dose heparin.

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“…Although DSCs appear to have a potent anti-inflammatory effect, it was not known whether the cells would be effective for myelopathy [9][10][11]14].…”

Section: Discussionmentioning

confidence: 99%

Treatment of radiculomyelopathy in two patients with placenta-derived decidua stromal cells

Sadeghi

Ersmark²,

Moretti

et al. 2019

Int J Hematol

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Mesenchymal stromal cells may reverse acute inflammatory disorders. The placenta is important in feto-maternal tolerance. We have used placenta-derived decidua stromal cells (DSCs) to treat graft-versus-host disease and found an immunomodulatory and anti-inflammatory effect. We here report the use of DSCs in two patients with radiculomyelopathy. The first patient was a 73-year old man treated with parotidectomy and irradiation for lymphoma of the neck. Following a Yersinia infection, he developed a radiculomyelopathy in C3/C4 and could not elevate his arms. The second patient was a 34-year old woman who was admitted 8 months after allogeneic hematopoietic stem cell transplantation due to hemolysis, impaired sensorium below arcus, and difficulty in ambulation. Following intravenous infusion of DSCs (1 × 10 6 /kg/infusion), the first patient could elevate his arms to the facial level. He experienced recurrent paralysis after 6 months, and the efficacy of four additional DSC infusions, at subsequent occasions, were limited and transient. The second patient was treated with two doses of DSCs (1 × 10 6 /kg/infusion). After cell infusion, she was able to stand on one leg, sensation in the belly normalized, and she was discharged. These two cases suggest that DSCs may be useful in the treatment of neuroinflammatory disorders.

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Placenta-Derived Decidua Stromal Cells for Hemorrhagic Cystitis after Stem Cell Transplantation

Cited by 29 publications

References 40 publications

Placenta-Derived Decidua Stromal Cells for Treatment of Severe Acute Graft-Versus-Host Disease

Placenta-Derived Decidua Stromal Cells for Treatment of Severe Acute Graft-Versus-Host Disease

Preclinical Toxicity Evaluation of Clinical Grade Placenta-Derived Decidua Stromal Cells

Treatment of radiculomyelopathy in two patients with placenta-derived decidua stromal cells

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