Stromal cells–are they really useful for GVHD?

Abstract

Mesenchymal stromal cells (MSCs) have immunomodulatory effects and are increasingly being used for the treatment of acute and chronic GVHD. Although they seem immuno-privileged, they induce alloresponses, but the risk of immunization is poorly characterized. After infusion, they first reach the lungs, liver and spleen, and are then difficult to trace. Several mechanisms are involved in stromal cells suppressing alloreactivity, such as induction of regulatory T cells, but whether or not this will also affect leukemic relapse or increase infections is not known. Although several encouraging pilot studies have been published, there have been few prospective randomized trials. There may be a bias in the literature, as negative results are seldom published, and there have been few comparative studies with other immunosuppressive regimens. Most animal models have failed to show any effect on GVHD. Several questions remain to be answered for optimization of stromal cell therapy. Which source is optimal-BM, fat, cord or decidua? Can stromal cells be replaced by exosomes, which culture conditions are most appropriate and at what passage and how frequently should cells be administered? More research is required to move stromal cell therapy forward to become an established treatment for acute and chronic GVHD.

Different Procoagulant Activity of Therapeutic Mesenchymal Stromal Cells Derived from Bone Marrow and Placental Decidua

“…Perinatal tissue-derived stromal cells have rapidly gained popularity since 2008 (11). We also switched to placenta-derived DSCs for clinical use (6)(7)(8), because these cells have more reproducible immunomodulatory effects than MSCs, they are much easier to obtain, and they have better expansion capacity (6,9). We now found that apart from already reported beneficial immunomodulatory and tropic properties, DSCs also have a smaller cell size and stronger hemostatic capacity, without eliciting any major adverse events, when prepared according to our optimized protocol.…”

“…Amniotic membrane has been used for successful management of extensive burn wounds and for wound reconstruction in Africa since the early twentieth century (13). Thus, similarly to BM-MSCs (14), the placenta has beneficial wound healing characteristics due to its anti-inflammatory, anti-microbial, anti-scarring, trophic, and hemostatic properties (3,9). This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction.…”

“…Few data are available on clinical experience with MSCs from bone marrow (BM) or from other sources in similar patient groups. Here we present a safety follow-up on placenta-derived decidual stromal cells (DSCs) (6)(7)(8) used as supportive immunomodulatory and regenerative therapy for patients with severe complications after hematopoietic stem cell transplantation (HSCT) (9).…”

Immunogenicity of Decidual Stromal Cells in an Epidermolysis Bullosa Patient and in Allogeneic Hematopoietic Stem Cell Transplantation Patients

“…Other possible antigens include xenobiotic serum components, such as bovine serum albumin (BSA) in fetal calf serum (FCS), which is used for expansion of MSCs. The immunogenicity of stromal cells in clinical settings has not been extensively studied [20], and the induction of alloantibodies has only been investigated in immunocompromised patients [21].…”

Mesenchymal stromal cells for prevention and treatment of graft-versus-host disease

“…In a very recent critical survey of the published literature by some of the authors of the very first clinical report [4], in 21 studies of treatment of acute GVHD and 10 studies of chronic GVHD involving, respectively, 190 and 61 patients, median 52 and 23% of complete responses (CRs) and partial responses (PRs), respectively, were observed, in the acute setting, while 26% CR and 48% PRs were reported in the chronic patients. In all patients, MSCs were of bone marrow origin, and no significant correlation has ever been found, among others, for autologous versus third-party origin.…”