Ensure the healthy future
Get advice from a leading specialist and find out how stem cells will help you.
Shiroor, Divya & Bohr, Tisha & Adler, Carolyn. (2020). Injury Delays Stem Cell Apoptosis after Radiation in Planarians. Current Biology. 10.1016/j.cub.2020.03.054.
Stem cells are continuously exposed to multiple stresses, including radiation and tissue injury. As central drivers of tissue repair and regeneration, it is necessary to understand how their behavior is influenced by these stressors. Planarians have an abundant population of stem cells that are rapidly eliminated after radiation exposure via apoptosis. Low doses of radiation eliminate the majority of these stem cells, allowing a few to remain . Here, we combine radiation with injury to define how stem cells respond to tissue damage. We find that a variety of injuries induced within a defined window of time surrounding radiation cause stem cells to outlast those in uninjured animals. Injury stimulates localized cell death adjacent to wounds , in the same regions where stem cells persist. This persistence occurs in the absence of proliferation. Instead, stem cells are retained near the wound due to delayed apoptosis, which we quantify by combining fluorescence-activated cell sorting (FACS) with annexin V staining. Pharmacological inhibition of the mitogen-activated protein (MAP) kinase extracellular signal-regulated kinase (ERK) prevents stem cell persistence after injury, implicating wound-induced ERK activity in this response. By combining radiation with injury, our work reveals a novel connection between dying cells and stem cells that remain. Furthermore, the ability to induce stem cell persistence after radiation provides a paradigm to study mechanisms that may contribute to unanticipated consequences of injury, such as tumorigenesis.
Gertz, Marc & Lacy, M & Inwards, D & Gastineau, Dennis & Tefferi, A & Chen, M & Witzig, Thomas & Greipp, P & Litzow, M. (2000). Delayed stem cell transplantation for the management of relapsed or refractory multiple myeloma. Bone marrow transplantation. 26. 45-50. 10.1038/sj.bmt.1702445.
The optimal timing of stem cell transplantation for multiple myeloma is controversial. Late stem cell collection is undesirable because of the inability to mobilize stem cells. We report on 64 recipients of stem cells collected within 1 year after diagnosis, none of whom had transplantation in plateau phase of their disease. Patients seen within 12 months after diagnosis received four cycles of standard vincristine, doxorubicin, and dexamethasone (VAD) chemotherapy and then had stem cells mobilized. Patients were then placed on maintenance vincristine, BCNU, melphalan, cyclophosphamide, and prednisone or melphalan and prednisone chemotherapy for 12 cycles. At the sign of first progression, transplantation occurred. Fourteen patients were refractory to VAD chemotherapy, 20 relapsed on maintenance chemotherapy, and 30 relapsed off chemotherapy. The time to platelet engraftment was not affected by the duration of stem cell cryopreservation or extent of chemotherapy exposure after mobilization. The complete response rate was 34%. The actuarial median survival from initial diagnosis, from transplant day 0, and post-transplant progression-free survival was 51, 20 and 11.4 months, respectively. The patient status at transplantation and percentage of plasma cells circulating in the blood at apheresis influenced post-transplant survival; circulating plasma cells, status at transplantation and plasma cell labeling index influenced progression-free survival. Response duration was shorter in patients relapsing on chemotherapy.