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Archive for the ‘stem cell biology and patient-specific’ Category


The Puzzle of Stem Cells and Cancer Stem Cells: The MIT Stem Cell Initiative

Reporter: Irina Robu, PhD

The MIT Stem Cell Initiative is looking to research fundamental biological questions about normal adult stem cells and their malignant counterparts, cancer stem cells. The MIT Stem Cell Initiative is applying new technologies and approaches in pursuit of this goal. In particular, the MIT Stem Cell Initiative has focused on the breast and colon, as these tissues are quite different from each other, yet each constitutes a major portion of cancer occurrence. The program purposes are to

(a) identify the stem cells and cancer stem cells in various tissues and tumor types,

(b) control how these cells change during aging or with disease progression and

(c) determine the similarities and differences between

  • normal cells, and
  • cancer stem cells,

with the goal of finding weaknesses in cancer stem cells that can be feasible and exact targets for treatment.

In due course, the ability to identify, purify, and establish several populations of stem cells and cancer stem cells could aid researchers to understand the biology of these cells, and learn how to exploit them more efficiently in regenerative medicine applications and target them in cancer.

Normal adult stem cells are undifferentiated cells within a tissue that divide to produce two daughter cells and divide periodically to replenish or repair the tissue. One of the two daughter cells remain in the stem cell state and the other adopts a partially differentiated state, then goes on to divide and differentiate further to harvest multiple cell types that form that tissue. The division process is through a precise process to ensure that tissues are restricted to the appropriate size and cell content.

Cancer stem cells perform the same division but, rather than differentiating, the additional cells produced by the second daughter cell amass to form the bulk of the tumor.

  • Cancer stem cells can regrow the tumor, and
  • are frequently resistant to chemotherapy.

This exclusive ability of normal and cancer stem cells to both self-renew and form a tissue or tumor is referred to by researchers as “stemness,” and has important implications for biomedical applications.

As a result, cancer stem cells are thought to be responsible for

  • tumor recurrence after remission, and also for the
  • formation of metastases, which account for the majority of cancer-associated deaths.

Accordingly, an anti-cancer stem cell therapy that can target and kill cancer stem cells is one of the holy grail of cancer treatment as means to suppress both tumor recurrence and metastatic disease. One of the important tasks to studying normal and cancer stem cells, and to ultimately harnessing that knowledge is developing the ability to identify, purify, and propagate these cells. Accordingly, the main goal in stem cell and cancer stem cell research is discovering ways to distinguish them, preferably by identifying unique surface markers that can be used to cleanse stem cell and cancer stem cell populations and enable their study.

New technologies are permitting the researchers to make significant headway in these investigations, progress that was not possible just a few years ago. Explicitly, they are using

  • a mixture of specially cultured cells,
  • highly controllable mouse models of cancer, and s
  • ingle-cell RNA sequencing and
  • computational analysis techniques that are extremely matched to extracting an excessive deal of information from the moderately small number of stem cells.

SOURCE

http://news.mit.edu/2018/mit-initiative-delves-into-stem-cell-biology-1015

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LIVE 2018 The 21st Gabay Award to LORENZ STUDER, Memorial Sloan Kettering Cancer Center, contributions in stem cell biology and patient-specific, cell-based therapy

REAL TIME Reporter: Aviva Lev-Ari, PhD, RN

AWARD LECTURE

Tue., Oct. 9, 2018
4:00 PM
Shapiro Campus Center Theater
Brandeis University

CURRENT WINNER

lorenzstuder.jpgLORENZ STUDER

MACARTHUR FELLOWS PROGRAM

Lorenz Studer

Stem Cell Biologist | Class of 2015

Pioneering a new method for large-scale generation of dopaminergic neurons that could provide one of the first treatments for Parkinson’s disease and prove the broader feasibility of stem cell–based therapies for other neurological disorders.

https://www.macfound.org/fellows/947/

118 publications on PubMed

https://www.ncbi.nlm.nih.gov/pubmed/?term=LORENZ+STUDER

 

PRESIDING

Dagmar Ringe Professor of Biochemistry, Chemistry and Rosenstiel Basic Medical Sciences Research Center

WELCOME

Lisa Lynch Provost and Maurice B. Hexter Professor of Social and Economic Policy Brandeis University

 

RESPONSE Lorenz Studer, MD Director, Center for Stem Cell Biology Memorial Sloan Kettering Cancer Center Member, Developmental Biology Program Memorial Sloan Kettering Cancer Center

Fully defined protocol for all ectodermal lineage

  • Nervous system: Forebrain, Midbrain, Spinal cord:
  • CNS lineage to PNS Lineage
  • Excitatory cortical neurons
  • cortical interneurons Astrocytes
  • microglia
  • Age-reset disease – late-onset during reprogramming – Is age reversible?
  • Loss of age-related markers
  • iPSC-derived cells yield stage cell upon differentiation
  • In vitro differentiation techniques: 2D Directed Differentiation 3D- Organoids
  • Graded MORPHOGEN SIGNALING
  • DOXYCYLINE: ISHH-ORGANIZER – 5 discrete forebrain regions
  • Building Human brain cells in 2D and in 3D
  • Organized cells –>>>  directed organoids –>> Organized Organoids
  • Parkinson, 1817 – Essay on Shaky Palsy (Niagrostaterial pathway)
  • Genetics and related dysfunction: affecting PD
  • Charckot, 1889
  • PD – new approach following drugs and deep brain stimulation failure in advanced disease: Fetal tissue transplant trials: Fetal Grafting
  • graft-induced dyskinesia
  • Long term, 15 years positive effects
  • Stem-cell-based regenerative therapy could transform PD therapy
  • 1995  Fetal DA neuron grafting for PD in Switzerland
  • 1998 – midbrain stem cell derived DA neuron
  • 200-2003 – Stem cell in brain implantation in WashDC
  • 2011 – Behavioral assays that are restored in mice
  • Optogenetics: manipulating – Light on the brain – control animal’s neurons
  • MOA of Graft function
  • Dopamine neurons – Stratium area of the human brain
  • From bench to bedside – WNT boost enhances EN1 expression
  • Neuron melanin induction
  • Manufacturing and QA testing: GMP – Off the shelf Allogenic Product
  • 1,000 human dose equivalents
  • cryopreserve
  • MSK-DA01 is highly enriched for mDA neuron precursors without detectable hESC Contaminants
  • FDA feedback and final steps to IND – PRE-IND MEETING: 2014, 2016
  • GLP STUDIES:
  • TUMORIGENICITY, BIODISTRIBUTION AND TOXISITY
  • HISTOLOGY OF FINAL PRODUCT
  • CLINICAL TRIAL DESIGN – STEM-PD – MSK and Weill Cornell Medicine
  • HLA expression is absent in edited iPSC with expression of HLA-E to block NK clearance
  • FUTURE: CRISPR
  • ATLaS-PD – assessing the longitudinal Symptoms/signs to moderate of severe stage
  • Development of a new PD therapy from Pluripotent Stem Cells
  • BlueRock Therapeutics – MSK-PD – Start up – $240Million funding
  • Stem cell based dopamine therapy for PD
  • Immunosuppression for 12 months
  • defined levodopa response > 45% improvement
  • Conclusions
  • Cell banks for clinical trials
  • NY state Stem cell science consortia

http://www.brandeis.edu/rosenstiel/images/pdfs/gabbay21program.pdf

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