SPOTLIGHTED RESEARCH REVIEW and COMMENTARY ARTICLES SCIENTIFIC PAPERS blood disease cancer cardiovascular disease development diabetes imaging immunology kidney disease lung disease nervous system diseases skeletal tissue engineering

This HSCI Research Update synthesizes the scientific work published by HSCI Principal Faculty each month. To continue receiving this newsletter, please register as an HSCI Affiliate or Friend by clicking here. If you are having problems viewing this newletter, click here to view it in your web browser. Spotlight In a research paper published in Science, investigators from the Harvard Stem Cell Institute, Children's Hospital Boston, Harvard Medical School, Brigham and Women's Hospital and Massachusetts General Hospital describe how mouse embryonic stem cells can be generated by parthenogenesis.

Histocompatible Embryonic Stem Cells by Parthenogenesis

In this study, George Daley and colleagues used unfertilized eggs of mice to create parthenogenetic embryonic stem cells. Parthenogenesis is a method of reproduction, common in plants and in some animals, in which the female can generate offspring without the contribution of a male. It doesn't normally occur in mice, but the team was able to induce unfertilized mouse eggs to develop through a series of chemical treatments, then generate embryonic stem cells.

Next, they identified those embryonic stem cells that shared with the egg donor the genes responsible for tissue matching, called the major histocompatibility complex (MHC). When they injected these selected embryonic stem cells into MHC-matched mice, a variety of specialized tissues formed, with no rejection and no need to suppress the recipients' immune system.

"This technique, if proven effective in humans, offers an efficient way of generating customized stem cell lines from women," says Daley. "It would eliminate tissue matching and tissue rejection problems, a major obstacle to successful tissue transplantation."

However, there are several potential limitations to embryonic stem cells generated by parthenogenesis. First, since parthenogenetic embryonic stem cells are made from eggs, the technique is only applicable to females. Also embryonic stem cells created through parthenogenesis have altered expression of imprinted genes, which has been linked with cancer and poor growth in some tissues. In addition, embryonic stem cells created through parthenogenesis may have some regions of their genome that contain duplicated copies of mutant genes that have been linked with malignancies or abnormal tissue growth.

"Right now this technique is useful for basic research, but we are hopeful that parthenogenetic cells might prove useful for therapies," Daley says. "Our cells produce normal tissues in mice, and there is a report in the clinical literature of a human patient whose blood was derived entirely from parthenogenetic cells. However, we'll have to demonstrate the safety and durability of cells derived from parthenogenetic embryonic stem cells before we could imagine any clinical use."

Daley's laboratory at Children's Hospital Boston is now trying to replicate its results with human eggs.

Kim K, Lerou P, Yabuuchi A, Lengerke C, Ng K, West J, Kirby A, Daly MJ, Daley GQ. Histocompatible Embryonic Stem Cells by Parthenogenesis. Science. 2006 Dec 14. Read Abstract.

Review and Commentary Articles

• Bonventre JV, Duffield JS. Response to 'Could tubular interstitium be a source of adult epithelial stem cells?' Kidney Int. 2006 Dec;70(11):2040-2041. Read Abstract.
• Rubin LL, de Sauvage FJ. Targeting the Hedgehog pathway in cancer. Nat Rev Drug Discov. 2006 Dec;5(12):1026-33. Read Abstract.
• Burns CE, Zon LI. Homing sweet homing: odyssey of hematopoietic stem cells. Immunity. 2006 Dec;25(6):859-62. Read Abstract.

Scientific Papers

Blood Disease

• Lasho TL, Pardanani A, McClure RF, Mesa RA, Levine RL, Gilliland DG, Tefferi A. Concurrent MPL515 and JAK2V617F mutations in myelofibrosis: chronology of clonal emergence and changes in mutant allele burden over time. Br J Haematol. 2006 Dec;135(5):683-7. Read Abstract.
• Kelly KA, Allport JR, Yu AM, Sinh S, Sage EH, Gerszten RE, Weissleder R. SPARC is a VCAM-1 counter-ligand that mediates leukocyte transmigration. J Leukoc Biol. 2006 Dec 18. Read Abstract.

Cancer

• Kobayashi S, Shimamura T, Monti S, Steidl U, Hetherington CJ, Lowell AM, Golub T, Meyerson M, Tenen DG, Shapiro GI, Halmos B. Transcriptional profiling identifies cyclin D1 as a critical downstream effector of mutant epidermal growth factor receptor signaling. Cancer Res. 2006 Dec 1;66(23):11389-98. Read Abstract.

Cardiovascular Disease

• Laustsen PG, Russell SJ, Cui L, Entingh-Pearsall A, Holzenberger M, Liao R, Kahn CR. Essential Role of Insulin and IGF-1 Receptor Signaling in Cardiac Development and Function. Mol Cell Biol. 2006 Dec 22. Read Abstract.
• Feng Y, Chen MH, Moskowitz IP, Mendonza AM, Vidali L, Nakamura F, Kwiatkowski DJ, Walsh CA. Filamin A (FLNA) is required for cell-cell contact in vascular development and cardiac morphogenesis. Proc Natl Acad Sci USA. 2006 Dec 26;103(52):19836-41. Read Abstract.

Development

• Kim K, Lerou P, Yabuuchi A, Lengerke C, Ng K, West J, Kirby A, Daly MJ, Daley GQ. Histocompatible Embryonic Stem Cells by Parthenogenesis. Science. 2006 Dec 14. Read Abstract.
• Jadhav AP, Cho SH, Cepko CL. Notch activity permits retinal cells to progress through multiple progenitor states and acquire a stem cell property. Proc Natl Acad Sci USA. 2006 Dec 12;103(50):18998-9003. Read Abstract.
• Bogunovic M, Ginhoux F, Wagers A, Loubeau M, Isola LM, Lubrano L, Najfeld V, Phelps RG, Grosskreutz C, Scigliano E, Frenette PS, Merad M. Identification of a radio-resistant and cycling dermal dendritic cell population in mice and men. J Exp Med. 2006 Nov 27;203(12):2627-38. Read Abstract.

Diabetes

• Ahn YB, Xu G, Marselli L, Toschi E, Sharma A, Bonner-Weir S, Sgroi DC, Weir GC. Changes in gene expression in beta cells after islet isolation and transplantation using laser-capture microdissection. Diabetologia. 2006 Dec 16. Read Abstract.
• Ahn YB, Xu G, Marselli L, Toschi E, Sharma A, Bonner-Weir S, Sgroi DC, Weir GC. Changes in gene expression in beta cells after islet isolation and transplantation using laser-capture microdissection. Diabetologia. 2006 Dec 16. Read Abstract.

Imaging

• Izmailova ES, Paz N, Alencar H, Chun M, Schopf L, Hepperle M, Lane JH, Harriman G, Xu Y, Ocain T, Weissleder R, Mahmood U, Healy AM, Jaffee B. Use of molecular imaging to quantify response to IKK-2 inhibitor treatment in murine arthritis. Arthritis Rheum. 2006 Dec 28;56(1):117-128. Read Abstract.
• Kim DE, Tsuji K, Kim YR, Mueller FJ, Eom HS, Snyder EY, Lo EH, Weissleder R, Schellingerhout D. Neural stem cell transplant survival in brains of mice: assessing the effect of immunity and ischemia by using real-time bioluminescent imaging. Radiology. 2006 Dec;241(3):822-30. Read Abstract.
• Saksena M, Harisinghani M, Hahn P, Kim J, Saokar A, King B, Weissleder R. Comparison of lymphotropic nanoparticle-enhanced MRI sequences in patients with various primary cancers. AJR Am J Roentgenol. 2006 Dec;187(6):W582-8. Read Abstract.
• Grimm J, Kircher MF, Weissleder R. Cell tracking : Principles and applications. Radiologe. 2006 Dec 23. German. Read Abstract.
• Nahrendorf M, Weissleder R. Advances in cardiovascular medicine through molecular imaging. Radiologe. 2006 Dec 23. German. Read Abstract.
• Nahrendorf M, Weissleder R, Ertl G. Does FXIII Deficiency Impair Wound Healing after Myocardial Infarction? PLoS ONE. 2006 Dec 20;1:e48. Read Abstract.

Immunology

• Butty V, Roy M, Sabeti P, Besse W, Benoist C, Mathis D. Signatures of strong population differentiation shape extended haplotypes across the human CD28, CTLA4, and ICOS costimulatory genes. Proc Natl Acad Sci USA. 2006 Dec 29. Read Abstract.

Kidney Disease

• Perianayagam MC, Liangos O, Kolyada AY, Wald R, Mackinnon RW, Li L, Rao M, Balakrishnan VS, Bonventre JV, Pereira BJ, Jaber BL. NADPH Oxidase p22phox and Catalase Gene Variants Are Associated with Biomarkers of Oxidative Stress and Adverse Outcomes in Acute Renal Failure. J Am Soc Nephrol. 2007 Jan;18(1):255-263. Read Abstract.

Lung Disease

• Ackerman KG, Wang J, Luo L, Fujiwara Y, Orkin SH, Beier DR. Gata4 is Necessary for Normal Pulmonary Lobar Development. Am J Respir Cell Mol Biol. 2006 Dec 1. Read Abstract.

Nervous System Diseases

• Prober DA, Rihel J, Onah AA, Sung RJ, Schier AF. Hypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish. J Neurosci. 2006 Dec 20;26(51):13400-10. Read Abstract.

Tissue Engineering

• Hannouche D, Terai H, Fuchs JR, Terada S, Zand S, Nasseri BA, Petite H, Sedel L, Vacanti JP. Engineering of Implantable Cartilaginous Structures from Bone Marrow-Derived Mesenchymal Stem Cells. Tissue Eng. 2006 Dec 1. Read Abstract.

The Harvard Stem Cell Institute is a scientific collaborative established to fulfill the promise of stem cell biology as the basis for cures and treatments for a wide range of chronic medical conditions.

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