1 3 DOI 10.1007/s12185-016-2014-2 Int J Hematol CASE REPORT Long-term survival of donor bone marrow multipotent mesenchymal stromal cells implanted into the periosteum of patients with allogeneic graft failure L. A. Kuzmina 1 · N. A. Petinati 1 · N. V. Sats 1 · N. J. Drize 1,2 · N. V. Risinskaya 1 · A. B. Sudarikov 1 · V. A. Vasilieva 1 · M. Y. Drokov 1 · E. D. Michalzova 1 · E. N. Parovichnikova 1 · V. G. Savchenko 1 Received: 4 February 2016 / Revised: 22 April 2016 / Accepted: 26 April 2016 © The Japanese Society of Hematology 2016 cases. In the vast majority of trails MSCs are administered intravenously and cannot be detected in the body after 7–10 days [2]. MSCs weakly express the CXCR4 receptor that binds the chemokine CXCL12 (SDF1) [3]. As a result, MSCs homing to bone marrow (BM) is very low [4, 5]. There is no published data about donor MSCs engraftment in humans. In patients with graft failure (GF) and long-term apla- sia after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the stromal microenvironment (SM) is fatally damaged and perhaps is unable to support hematopoiesis. Leukemic cells and chemotherapy used during allo-HSCT damage BM niches and change the SM [6, 7]. MSCs are involved in the formation of niches for hematopoietic stem cells and support hematopoiesis [8]. We can assume that donor MSCs may be able to repair HSC niches. In this study, three patients with GF after allo-HSCT had hemat- opoietic stem cells donor MSCs directly implanted into the bone to restore their SM. Patients and methods A randomized study for acute graft versus host dis- ease prophylaxis with MSCs has been conducted by the National Research Center for Hematology, Moscow, Russia [9–11]. MSCs were developed for each patient from their individual BM donor. There was long-term BM aplasia for more than 3 months observed in 3 patients with GF following allo-HSCT. All the patients received a second allo-HSCT with MSCs from the donor BM. The MSCs were injected under local anes- thesia in the iliac crest that is, directly into the bone marrow in the trabecular bone area. All patients provided informed consent. The implanted MSCs from several passages were Abstract The present study involved three patients with graft failure following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We obtained multipotent mes- enchymal stromal cells (MSCs) from the original hemat- opoietic cell donors and implanted these cells in the peri- osteum to treat long-term bone marrow aplasia. The results showed that in all patients endogenous blood formation was recovered 2 weeks after MSC administration. Donor MSCs were found in recipient bone marrow three and 5 months following MSC implantation. Thus, our findings indicate that functional donor MSCs can persist in patient bone marrow. Keywords Allogeneic hematopoietic stem cell transplantation (allo-HSCT) · Graft failure · Multipotent mesenchymal stromal cells (MSCs) · Periosteal implantation Introduction Human multipotent mesenchymal stromal cells (MSCs) are extensively used for cell therapy due to their unique immunomodulating capacity and differentiating abilities [1]. Mechanism of MSCs action in vivo is obscure in most Electronic supplementary material The online version of this article (doi:10.1007/s12185-016-2014-2) contains supplementary material, which is available to authorized users. * N. J. Drize ndrize@yandex.ru 1 National Research Center for Hematology, Moscow, Russia 2 Noviy Zikovsky pr, 4, Moscow 125167, Russia