Human mesenchymal stem cells modulate allogeneic immune cell responses

Mesenchymal stem cells (MSCs) are a heterogeneous subset of stromal stem cells that can be isolated from many adult tissues. They can differentiate into cells of the mesodermal lineage, such as adipocytes, osteocytes and chondrocytes, as well as cells of other embryonic lineages. MSCs can interact with cells of both the innate and adaptive immune systems, leading to the modulation of several effector functions. After in vivo administration, MSCs induce peripheral tolerance and migrate to injured tissues, where they can inhibit the release of pro-inflammatory cytokines and promote the survival of damaged cells. This Review discusses the targets and mechanisms of MSC-mediated immunomodulation and the possible translation of MSCs to new therapeutic approaches.

Mesenchymal stem cells in health and disease

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(04)16104-7.pdf

Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(08)60690-X.pdf

Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study.

https://www.exphem.org/article/S0301-472X(01)00769-X/pdf

Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo.

PURPOSE: Multipotential mesenchymal stem cells (MSCs) are found in human bone marrow and are shown to secrete hematopoietic cytokines and support hematopoietic progenitors in vitro. We hypothesized that infusion of autologous MSCs after myeloablative therapy would facilitate engraftment by hematopoietic stem cells, and we investigated the feasibility, safety, and hematopoietic effects of culture-expanded MSCs in breast cancer patients receiving autologous peripheral-blood progenitor-cell (PBPC) infusion. PATIENTS AND METHODS: We developed an efficient method of isolating and culture-expanding a homogenous population of MSCs from a small marrow-aspirate sample obtained from 32 breast cancer patients. Twenty-eight patients were given high-dose chemotherapy and autologous PBPCs plus culture-expanded MSC infusion and daily granulocyte colony-stimulating factor. RESULTS: Human MSCs were successfully isolated from a mean ± SD of 23.4 ± 5.9 mL of bone marrow aspirate from all patients. Expansion cultures generat...

Rapid Hematopoietic Recovery After Coinfusion of Autologous-Blood Stem Cells and Culture-Expanded Marrow Mesenchymal Stem Cells in Advanced Breast Cancer Patients Receiving High-Dose Chemotherapy

https://www.exphem.org/article/S0301-472X(99)00101-0/pdf

Bone marrow-derived mesenchymal stem cells remain host-derived despite successful hematopoietic engraftment after allogeneic transplantation in patients with lysosomal and peroxisomal storage diseases

Purpose: Multipotential mesenchymal stem cells (MSCs) are found in human bone marrow and are shown to secrete hematopoietic cytokines and support hematopoietic progenitors in vitro. We hypothesized that infusion of autologous MSCs after myeloablative therapy would facilitate engraftment by hematopoietic stem cells, and we investigated the feasibility, safety, and hematopoietic effects of culture-expanded MSCs in breast cancer patients receiving autologous peripheralblood progenitor-cell (PBPC) infusion. Patients and Methods: We developed an efficient method of isolating and culture-expanding a homogenous population of MSCs from a small marrow-aspirate sample obtained from 32 breast cancer patients. Twenty-eight patients were given high-dose chemotherapy and autologous PBPCs plus culture-expanded MSC infusion and daily granulocyte colony-stimulating factor. Results: Human MSCs were successfully isolated from a mean 6 SD of 23.4 6 5.9 mL of bone marrow aspirate from all patients. Expansion cultures generated greater than 1 3 10 6 MSCs/kg for all patients over 20 to 50 days with a mean potential of 5.6 to 36.3 3 10 6 MSCs/kg after two to six passages, respectively. Twenty-eight patients were infused with 1 to 2.2 3 10 6 expanded autologous MSCs/kg intravenously over 15 minutes. There were no toxicities related to the infusion of MSCs. Clonogenic MSCs were detected in venous blood up to 1 hour after infusion in 13 of 21 patients (62%). Median time to achieve a neutrophil count greater than 500/mL and platelet count > 20,000/mL untransfused was 8 days (range, 6 to 11 days) and 8.5 days (range, 4 to 19 days), respectively. Conclusion: This report is the first describing infusion of autologous MSCs with therapeutic intent. We found that autologous MSC infusion at the time of PBPC transplantation is feasible and safe. The observed rapid hematopoietic recovery suggests that MSC infusion after myeloablative therapy may have a positive impact on hematopoiesis and should be tested in randomized trials. J Clin Oncol 18:307-316. © 2000 by American Society of Clinical Oncology.

Rapid H ematopoietic R ecovery A fter C oinfusion o f Autologous-Blood S tem C ells a nd C ulture-Expanded Marrow M esenchymal S tem C ells i n A dvanced B reast Cancer P atients R eceiving H igh-Dose C hemotherapy

Stephanie M. Dyhouse

Papers

Rapid Hematopoietic Recovery After Coinfusion of Autologous-Blood Stem Cells and Culture-Expanded Marrow Mesenchymal Stem Cells in Advanced Breast Cancer Patients Receiving High-Dose Chemotherapy

Bone marrow-derived mesenchymal stem cells remain host-derived despite successful hematopoietic engraftment after allogeneic transplantation in patients with lysosomal and peroxisomal storage diseases

Rapid H ematopoietic R ecovery A fter C oinfusion o f Autologous-Blood S tem C ells a nd C ulture-Expanded Marrow M esenchymal S tem C ells i n A dvanced B reast Cancer P atients R eceiving H igh-Dose C hemotherapy