Pancreatic acinar cells regenerate but do not transdifferentiate
It has been suggested that pancreatic acinar cells might serve as progenitors for generating pancreatic islets as a way to increase the insulin-producing 
-cell mass in patients with diabetes. However, new research published in the April 2007 issue of the Journal of Clinical Investigation suggests that although acinar cells seem to have the capacity to regenerate, they are unable to serve as progenitors for cells. The authors used an in vivo lineage tracing approach to determine the plasticity potential of pancreatic acinar cells. They developed an acinar cell–specific inducible Cre recombinase transgenic mouse that, when mated with a reporter strain and pulsed with tamoxifen, gave rise to permanent and specific labeling of acinar cells and their progeny. The workers failed to observe any chase of the labeled cells into the endocrine compartment following pancreatic injury, indicating that acinar cells do not normally transdifferentiate into islet cells in vivo in adult mice. In contrast, they observed a substantial role for replication of preexisting acinar cells in the regeneration of new acinar cells after partial pancreatectomy. The results indicate that mature acinar cells harbor a facultative acinar but not endocrine progenitor capacity. (J Clin Invest 117: 971–977, 2007; doi:10.1172/JCI29988)
Treatment-induced growth factor causes cancer progression
In advanced cancer, antitumor therapies often work only partially or not at all, and tumors progress following treatment. A new study has linked a treatment-induced growth factor to cancer progression. The study, published in the May 2007 issue of the Journal of Clinical Investigation, shows that radiation and chemotherapy increase circulating levels of transforming growth factor (TGF)-, circulating cancer cells, and tumor metastases in a mouse model of metastatic breast cancer. Blocking TGF- in the model prevented tumor metastases, suggesting that TGF- inhibitors may be clinically useful in combination with primary therapies. The workers had previously shown that a brief induction of TGF- in a transgenic mouse model of breast cancer dramatically accelerated metastasis. Radiation therapy and the chemotherapeutic agents doxorubicin and docetaxel all increased TGF- concentrations and accelerated metastasis, an effect that was blocked by neutralizing antibodies directed against TGF-. Similar results not reported in this article have been observed with small-molecule inhibitors of the TGF- type I receptor kinase. The authors speculate that patients who have treatment-induced increases in TGF- may not respond as well to the anticancer therapy as those who do not. Increased circulating and/or tumor TGF- in response to treatment may be a marker of tumors destined to progress rapidly after therapy. Thus, patients with such tumors might benefit from the addition of TGF- inhibitors to the primary therapy. Several TGF- inhibitors are currently in early-stage clinical trials. (J Clin Invest, published online 9 April 2007; doi:10.1172/JCI30740)
Stem cell transplantation to treat type 1 diabetes
Type 1 diabetes mellitus (DM) results from a cell-mediated autoimmune attack against pancreatic cells. -cell preservation has been shown to be an important strategy for the management of type 1 DM. A new study published in the 11 April 2007 issue of the Journal of the American Medical Association now shows that a therapy that includes stem cell transplantation can lead to extended insulin independence in diabetic patients. The workers examined the effect of high-dose immunosuppression followed by autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) to preserve -cell function in 15 newly diagnosed patients with type 1 DM. AHST, which uses a patient's own blood stem cells, involves the removal and treatment of the stem cells and their return to the patient by intravenous injection. During a 7- to 36-month follow-up, 14 patients became insulin-free (one for 35 months, four for at least 21 months, seven for at least 6 months; two with late response were insulin-free for 1 and 5 months, respectively). Among those, one patient resumed insulin use 1 year after AHST. The only severe adverse effects were pneumonia in one patient and endocrine dysfunction in two others. Further studies are necessary to confirm the role of this treatment in changing the natural history of type 1 DM and to evaluate the contribution of hematopoietic stem cells to this change. (JAMA 297: 1568–1576, 2007; doi:10.1001/jama.297.14.1568)
Study identifies cochlear stem cells
In addition to loud noise, certain cancer drugs or genetic factors can cause hearing loss in humans due to loss or faulty development of the sensory hair cells inside the ear. Lost hair cells are not replaced, and their destruction leads to permanent hearing loss. New research published in the February 2007 issue of Developmental Neuroscience suggests new ways of treating hearing loss. Workers have isolated "cochlear stem cells" from the inner ear that are already primed for development into ear-related tissue. Previous work with young-adult mouse cochlear tissue showed expression of genes normally found in stem cells and neural progenitors, suggesting that the cochlea harbors stem cells and neural precursor cells. The new study provides further evidence for the existence of cochlear stem cells in the mouse cochlea by confirming the ability of the cells to form "stem cell" spheres in culture and by characterizing these cells in terms of neural and hair cell development using a panel of stem cell development and hair cell markers. The formation of spheres from early postnatal cochlear tissues and their expression of a wide range of developmental markers unique to hair cells confirm the possibility that self-supporting hair cell precursors exist in or can be derived from the postnatal mammalian cochlea. The authors now plan to screen for compounds that can promote regeneration of hair cells from the stem cells in vitro. (Dev Neurosci 29: 251–260, 2007; doi:10.1159/000096415)
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