Sundin et. al. (2007), No alloantibodies against mesenchymal stromal cells, but the presence of anti-fetal calf serum antibodies, after transplantation in allogeneic hematopoietic stem cell recipients. Haematologica. 2007 Sep; 92(9):1208-15. Epub 2007 Aug 1.
The paper describes a study that aimed to investigate whether MSC transplantation in hematopoietic stem cell transfer (HSCT) patients is complicated by humoral immunity against the cells. The study involved the flow cytometric and ELISA-mediated analysis of serum collected from 12 patients pre and post-infusion of MSCs. While antibodies against fetal calf serum (a component of the MSC culture media) were found in the sera of a few patients, no antibodies were found to have been synthesized against the MHCs. This indicates that there is little risk of a humoral immune response being triggered against MSC therapy.
Herrmann et. al. (2011), Mesenchymal stromal cell therapy for steroid-refractory acute and chronic graft versus host disease: a Phase 1 study. Int J Hematol. 2012 Feb; 95(2):182-8. Epub 2011 Dec 20.
The paper describes a phase 1 clinical study pertaining to the use of bone marrow-derived MSCs for the treatment of acute and chronic graft versus host disease (AGvHD and CGvHD). The study involved the infusion of a total of 109 doses of donor-derived MSCs to 19 patients, of which 12 suffered from AGvHD and 7 from CGvHD. Among the patients suffering from AGvHD, 7 exhibited a completely positive response (loss of all symptoms), 4 exhibited a partial response (improvement by one grade), and 1 patient did not respond to treatment. These response rates indicated that MSCs could be used to treat AGvHD in combination with steroid therapy.
Forbes et. al. (2013), A Phase 2 study of allogeneic mesenchymal stromal cells for luminal Crohn’s disease refractory to biologic therapy, Clin Gastroenterol Hepatol. 2014 Jan; 12(1):64-71. Epub 2013 Jul 19.
The paper describes a clinical study pertaining to the use of allogeneic MSCs to treat biologic-refractory luminal CD. The study involved administering allogeneic MSCs to 16 patients, out of which a clinical response was found to occur in 12, and endoscopic improvement (i.e., a substantial decrease in Crohn’s Disease endoscopic index of severity) was observed in 7. The study proved that the use of MSCs offers an edge over peripheral stem cells, which require cytotoxic myelo-conditioning and have resulted in long-term remission of CD in only a few patients.
Chambers et. al. (2017), Mesenchymal stromal cell therapy for chronic lung allograft dysfunction: results of a first‐in‐man study. Stem Cells Transl Med. 2017 Apr; 6(4): 1152–1157.
The paper describes a phase 1 clinical study pertaining to the use of MSCs for the treatment of CLAD – also called chronic lung transplant rejection. The study involved the infusion of MSCs to 10 patients suffering from advanced CLAD – which resulted in a steep reduction in the forced expiratory volume in one second for all patients (i.e., from 120 ml/month pre-infusion to 30ml/month post-infusion). This suggests that MSCs can effectively be used for treating not only patients with advanced CLAD, but also patients suffering from new-onset CLAD.
Morrison et. al. (2017), Cranial reconstruction using allogeneic mesenchymal stromal cells: A phase 1 first-in-human trial. J Tissue Eng Regen Med . 2018 Feb; 12(2):341-348. Epub 2017 Aug 23.
The paper describes a phase 1 clinical study pertaining to the use of MSCs for cranial reconstruction in patients who have recently undergone craniectomy. The study involved seeding of MSCs onto a rigid absorbable polymer layer placed on specialized 3D-printed molds, followed by the implantation of these polymer meshes into a patient’s cranium. While the implant did result in bone formation in the initial months, bone resorption was observed in all 3 patients after 12 months – possibly due to the reduction in rigidity of the polymer over time. The study indicates that MSCs – in combination with a relatively rigid culture scaffold (e.g., ceramic and/or titanium mesh) – may constitute a cost-effective treatment for bone reconstruction.
Armitage et. al. (2018), Mesenchymal stromal cell infusion modulates systemic immunological responses in stable COPD patients: a phase I pilot study, European Respiratory Journal 2018 51: 1702369.
The paper describes a phase 1 clinical study that aimed to understand the systemic changes induced by the infusion of MSCs in patients suffering from COPD. The researchers studied the biodistribution of MSCs post-infusion and correlated it with observed immunological changes (for example, an increase in the number of circulating T-cells – which is brought on by the release of trophic factors from injected MSCs.) The study proves that even though MSCs have not been found to improve spirometric readings in past studies, they may prove to be effective in reducing inflammation in COPD patients.
Chambers (2019), Bronchiolitis obliterans syndrome ‘endotypes’ in hematopoietic stem cell transplantation. Editorial Respirology. 2019 May; 24(5):408-409. Epub 2019 Feb 7.
The article briefly reviews a few papers related to the classification of phenotypes associated with bronchiolitis obliterans syndrome (BOS) – a serious respiratory complication that occurs as a result of an organ transplant and leads to irreversible narrowing of the small airway due to the deposition of scar tissue. The author predicts that while the different phenotypes have not been recorded, analyzed, and classified well over the years, the use of modern tools, such as big data and machine learning software, is likely to help classify these phenotypes in a better manner, thus facilitating the design of precision medicine for patients suffering from BOS.
Ciccocioppo et. al. (2019), Perspectives of the International Society for Cell & Gene Therapy Gastrointestinal Scientific Committee on the intravenous use of mesenchymal stromal cells in inflammatory bowel disease (PeMeGi), Cytotherapy. 2019 Aug; 21(8):824-839. Epub 2019 Jun 11.
The paper reviews several research articles and clinical studies that pertain to the use of intravenously infused MSCs to treat inflammatory bowel disease (IBD.) It highlights a major change in approach to measuring the efficacy of treatment over the years, wherein companies now look to achieve mucosal healing (indicated by decreased hospitalization and reduced need for surgery) instead of long-term clinical remission. It further highlights the most appropriate (and/or commonly used) methods of preparing these therapies, administering them to patients, and/or designing a treatment regimen. Besides, it recommends that data from all future studies should be standardized and combined in a database to allow for the selection of clinically relevant biomarkers.
Purtill et. al. (2020), Early cessation of a randomized study in acute graft versus host disease: upfront mesenchymal stromal cells with corticosteroids versus corticosteroids alone. Bone Marrow Transplant. 2020 Nov; 55(11):2199-2201. Epub 2020 May 27.
The paper summarises and discusses the results of a randomized study pertaining to the use of MSCs for the treatment of AGvHD – along with corticosteroids – right after diagnosis. The results – provided in the form of survival rates 12 months post randomization (53% in the test arm and 77% in the control arm) – indicated that the treatment was not effective and resulted in the data safety and monitoring board demanding early cessation of the study. The paper discusses these results and lists various factors, (e.g., the inflammatory status of the patient and interference due to concomitant corticosteroid therapy), which could have interfered with the treatment and skewed results.