Mesenchymal stem cells expanded in vitro with human serum for the treatment of acute and chronic graft-versus-host disease: results of a phase I/II clinical trial

Abstract

MSC expansion procedure, cell characterization and obtaining platelet lysate were performed according to standard procedures and are shown in the Online Supplementary Appendix. Patients' characteristics and MSC infusionOverall, 18 patients diagnosed with either acute (n=10) or chronic (n=8) GVHD refractory to prior treatment were included in the study once written informed consent had been obtained. Refractory GVHD was defined as progression or absence of response to last treatment. Patients' characteristics are summarized in Table 2. Eleven patients had received reduced intensity conditioning and 6 received myeloablative conditioning. Fourteen patients had received hematopoietic stem cells from an unrelated donor and 7 received them from an HLA-mismatched donor. Eight patients had received GVHD prophylaxis based on a calcineurin inhibitor plus methotrexate.Inclusion criteria were: patients who had undergone an allogeneic stem cell transplant and developed GVHD refractory to conventional treatment; adequate cardiac and pulmonary functions; aged between 18 and 65 years; signed informed consent from patient and donor. Exclusion criteria were: patients who did not fulfill all of the inclusion criteria; progression of the hematologic disease; active infection; women who were either pregnant or at risk of pregnancy. The study was conducted between February 2007 and December 2009.Patients received 1-2x10 6 MSCs/kg intravenously in a single dose. Eventually, when a partial response was obtained or in the case of relapse after achieving complete remission, patients could receive a second dose of MSCs at least two weeks after the first infusion. Patients who were receiving 6-methylprednisolone were kept on the same doses for at least seven days after MSC infusion and a taper of 10% every five days was planned later when there was a response. Other immunosuppressive drugs were managed according to the criteria of the attending physician. Response to therapy was measured according to previously reported criteria. [9][10][11] Patients were taken off the study if fewer than 1x10 6 MSCs/kg were obtained after eight weeks of expansion. All patients receiving at least one dose of MSCs were included in the safety and efficacy analysis.The treatment protocol was reviewed and approved by the local authorities and ethical committee of all participanting centers.Mesenchymal cells for graft vs. host disease treatment haematologica | 2011; 96 (7) 1073 Statistical analysisVariables of the expansion procedure were analyzed from the day of inclusion in the trial, i.e. the day when informed consent was signed. Mean and median values and their corresponding 95% confidence intervals (CIs) and ranges were calculated for each continuous variable. Student's two-sample t test and Pearson's X 2 test were used to compare continuous and qualitative variables. In those comparisons where the number of cases precluded the use of parametric tests, the Mann-Whitney test and Fisher's exact test were used. To analyze patient outcome after infusi...

Stromal cells–are they really useful for GVHD?

“…However, this treatment needs to be optimized, combining it with the right immunosuppressive therapies. We need to learn more about the therapeutic potential of stromal cells in order to understand their mechanistic functions Adipose tissue 83,88 Umbilical cord 83,89 Placenta-derived decidua 83,90 Exosomes from stromal cells 76 Expansion media FCS 8,9,[82][83][84][85][86][87] Platelet lysate medium 83,85 AB serum 84 Regulatory T cells CD4 þ in the clinical setting. We have learnt that they are immunosuppressive and that they have regenerative properties, but so far these traits have only been confirmed in vitro.…”

“…83 Most centres used MSCs expanded in FCS, but expansion of MSCs in platelet lysate medium and human AB serum was also reported. 84,85 There have been few randomized studies using MSCs. Osiris Therapeutics, Inc. used expanded MSCs, Prochymal, for acute GVHD of grades II-IV.…”

Mesenchymal Stem Cells: The First Approved Stem Cell Drug in Japan

“…8 The treatment protocol was basically the same as described above, and the observation time was pro- Many prospective studies using MSCs for SR-aGVHD have been conducted Table 1 . 7,8,18,[20][21][22][24][25][26][27][28][29][30][31][32][33][34] As shown, the patients who were enrolled and the defined endpoints varied.…”

Перспективы Применения Препаратов На Основе Мезенхимальных Стволовых Клеток В Терапии Пост-Трансплантационных Осложнений, Связанных С Иммунной Несовместимостью

“…Большая часть проводящихся в настоящее время клинических исследований -это исследования фазы 2 или фазы 1/2, но есть и исследования фазы 3. Опубликованы данные лишь некоторых из исследований, начавшихся ранее, и показавшие, что метод безопасен и обладает определенной эффективностью [8,37,23]. Недавно вышедший первый мета-анализ данных клинических исследований [41] также показывает безопасность метода, а в отношении эффективности содержит противоречивые данные.…”