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Recent MSU Stem Cell Research Projects

This webpage describes some MSU research involving stem cells that has been or is being conducted.

Study of Conditions or Diseases

Attention Deficit Hyperactivity Disorder (ADHD)

  • Attention Deficit Hyperactivity Disorder: studying a number of complex genetic diseases, which primarily use high throughput analysis of genomic variation.

Cancer

  • Human carcinogenesis, especially breast cancer: developing various adult stem cells for clinical application. The chemical modification of cell culture conditions to induce and maintain pluripotency, especially the modulation of cellular redox to enhance the expression of pluripotency genes such as Oct-4.
  • Human breast epithelial stem cells: isolating the cells that express Oct-4 and estrogen receptor alpha and are deficient in gap junctional intercellular communication similar to most human breast carcinomas. These cells have been shown to be more susceptible to telomerase activation, immortalization, and neoplastic transformation, providing strong evidence for the stem cell theory of carcinogenesis.
  • Genetic toxicology and oncology: determining the cellular mechanisms by which nutrition, oxidative stress, and environmental and food-borne contaminants affect cell proliferative, differentiation, and apoptotic processes that ultimately cumulates into states of human diseases such as cancer.
  • Cancer biomarkers: Developing new non-invasive, accurate clinical biomarkers for early detection of cancers, particularly for cancers from hard to treat, well-advanced tumors, such as those within the pancreas.
  • Cancer treatments: identifying adult human stem cells and their role as “targets” for the origin of “cancer stem cells” is providing strategies for cancer prevention and cancer therapy.

Hearing Loss

  • Genetic hearing loss: identifying genes required for normal hearing and characterization of the mutations that cause hearing loss. Linkage mapping in affected families is used to identify genes causing hearing loss. Characterization of the causative mutations is performed using cell culture, animal models, and in vitro systems.

Hutchinson-Gilford Progeria-Premature Syndrome

  • Hutchison Gilford progeria (HGPS): studying this premature aging syndrome, in which the majority of cases are caused by a single mutation in exon 11 in the gene encoding lamin A. Lamin A, being one of the components of the nuclear envelop of cells, maintains the normal architecture of the nucleus. A mutation of the lamin A gene leads to the distortion and folding of the nuclear membrane, which causes genome instability, DNA repair defects, and altered gene expression. The nuclear lamina mutation also occurs in normal physiological aging. Because aging has been associated with abnormal stem cell homeostasis, the hypothesis is that the nuclear abnormality could have an important impact on stem cell function and in the role of adult stem cells on diseases of aging. To test this hypothesis, the proliferation, differentiation and apoptosis in stem cells and cancer cells which exhibit nuclear lamina defects after being transfected with mutated lamin A genes are being examined.

Parkinson’s Disease

  • Neural mechanisms: exploring the neural mechanisms associated with development of adverse consequences of Parkinson’s Disease and treatment (such as stress, depression and levodopa-induced dyskinesias) and mechanisms associated with translational therapeutics, including progenitor cell transplantation.
  • Link between aging and Parkinson’s Disease: working on neural progenitor cells, with a focus on mechanisms associated with the capacity of these cells to exert neuroprotection for the dopamine system endangered in Parkinson’s disease when transplanted in an undifferentiated state. These grafted cells alter their local environment and stimulate resident neural stem cells to proliferate and migrate, all in support of neural protection and repair.

Study of Cell Mechanics

Cell System Injury Sites

  • Nanofibrillar scaffold: understanding nanoscale properties that, in different proportions, serve as the primary cues for the re-establishment of cell systems that rely on nanofibrillar scaffold in their native environment. Injury sites that are supplied with bridge environments can regenerate and re-establish functional connection with healthy surrounding tissue when provided with physically and chemically mimetic bridges for the extracellular matrix using physiological scaffolding that directs cells to either proliferate or differentiate. Alternatively, such scaffolds can be used to replace lost tissue through grafting of exogenous cells, including pluripotent stem cells that receive their selective development cues from the bridge environment.

Epigentics

  • Halogenated aromatics: studying the mechanisms of epigenetic effects of halogenated aromatics; isolation and characterization of precursor cells from neonatal rat cerebellum; pluripotent stem-like cells from adult human pancreatic tissue.
  • Developmental epigenetics and reproductive biology: understanding the genetic and epigenetic basis for cellular differentiation in the mammalian embryo, which has implications in assisted reproductive technologies (ART) and cellular reprogramming for cell replacement therapies, as well as cancer.

Gene Transfer

  • Gene transfer: exploring the feasibility of gene transfer to cure human genetic and nongenetic diseases, including diseases affecting the liver, eye, hearing apparatus, muscles, heart, coronary arteries, as well as its ability to improve certain aspects of cancer therapies.

Molecular Aging

  • Oocyte genomic instability in aging and chemotherapy: identifying the interaction between Bax and Rad51, a protein involved in cell viability and in DNA repair, and how this determines survival of female germ cells during aging and after doxorubicin treatment; ceramide modulation of death in germ cells of aging females, to determine the molecular basis for sphingolipid (e.g., ceramide) modulated increased germ cell loss with age; role of sphingolipids in doxorubicin trafficking, to elucidate the details of sphingolipid (e.g., ceramide) and doxorubicin movement in cells undergoing apoptosis; and understanding the novel role of cell death in fertilization.

Study of Stem Cells

Isolation of Adult Human Stem Cells

  • Normal adult human stem cells: developing and characterizing adult human stem cells including kidney, breast epithelial, pancreatic, liver, gastric and mesenchymal stem cells.
  • Safety assessment uses: characterizing the use of human adult stem cells for drug discovery of toxicological safety assessment.
  • Novel development techniques: finding ways to develop many human adult stem cells, including kidney, mammary epithelial, pancreatic, gastric, liver, endometrial and adipose-derived mesenchymal stem cells.

Neural Stem Cells

  • Survival and death of neural stem cells: understanding the mechanisms regulating the survival and death of neural stem cells, which may shed light on the potential application of these cells for repair of the neuronal damage; uses adult neural stem cells derived from rat hippocampus to find the signaling mechanisms underlying neural stem cell apoptosis.

Pancreatic Stem Cells

  • Self-renewal and differentiation: isolating and characterizing human pancreatic stem cells and comparison of gene expression of the stem cells and their differentiated progeny, with special interest in the pathways that control pancreatic stem cell self-renewal and differentiation.

Pluripotent Stem Cells

  • Cellular dedifferentiation processes: understanding cellular dedifferentiation processes that would eventually allow for the generation of pluripotent stem cells without the use of embryos or recombinant DNA.
  • New hESC lines from minority populations: generating new lines under xenofree conditions and current regulatory guidelines to promote their future use in clinical trials. Improving the quality, number and ethnic diversity of hESC lines derived under current national regulatory guidelines will provide an extended resource of these cells for possible therapeutic applications and for basic research with ethnically diverse lines. (Current human embryonic stem cells (hESC) lines reflect limited ethnic diversity, particularly among minorities, and many are unable to be used in therapies due to culturing artifacts, high passage number or regulatory restrictions.)

For more information about MSU stem cell research projects, contact Stemcell@msu.edu.