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Contact Information
Photo of Christine Finck, M.D.
Christine Finck, M.D.

Center for Vascular Biology
University of Connecticut Health Center
263 Farmington Avenue
Farmington, CT 06030-3501

Phone: 860-679-2374/860-545-9520
Fax: 860-679-1201
Email: cfinck@connecticutchildrens.org

Finck Lab

 

Lab Members

Photo of Dr. Finck's lab members

Christine Finck, M.D.
Principal Investigator
Associate Professor
Email: cfinck@ccmckids.org
Phone: 860-679-2374/860-545-9520

Stephanie Vadasz, Ph.D.
Postdoctoral Fellow
Email: vadasz@uchc.edu
Phone: 860-679-7845

 

Todd Jensen, M.S.
Research Associate
Email: tjensen@uchc.edu
Phone: 860-679-7845

 


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Research Interests

Research in the Finck lab focuses on pediatric lung disease, specifically hypoplastic or underdeveloped lungs in infants. The goal of the lab is to investigate cell therapy and tissue engineering options for potential clinical treatment.

Common pediatric disease associated with under developed lungs are respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD). RDS is a life-threatening lung disorder commonly seen in premature babies, in which a baby’s lungs do not produce surfactant and connect exchange air. BPD is a chronic lung disease that is seen most often in severely premature babies who developed RDS. About 30% of these severely premature babies are diagnosed with the disease. Because the under-developed lungs cannot fully recover from the early damage, these conditions could particularly benefit from improvements in regenerative medicine techniques.

One of the many promising approaches to developing patient-specific cell therapy involves the isolation or reprogramming of the patient’s own cells, thereby reducing any rejection responses as well as the need for long-term immunosuppressive treatment. Our lab currently is working to reprogram human fibroblasts using an excisable lentiviral cassette therefore resulting in transgene-free iPS cells. Induced pluripotent stem cells are cells that have been induced to express pluripotency markers by infection with a virus. This approach allows researchers to reprogram adult cells, like fibroblasts, into pluripotent cells that can then be further differentiated into lung-type cells.

Amniotic fluid stem cells are a newly discovered source of multi-potent type stem cells that can be potentially used for cell therapy. These cells may not require reprogramming like iPS cells. These cells can be obtained prior to the birth of a child, therefore allowing researchers time to develop patient-specific therapy. We are working closely with Hartford Hospital and Connecticut Children’s Medical Center to obtain amniotic fluid and fibroblast samples to continue investigating these patient specific therapeutic options.

Given the need for lung transplants and the shortage of donor lungs, engineering whole organs is another goal of the Finck lab. The shortcomings of donor lung transplantation are well catalogued, specifically, the shortage of suitable donor lungs, the high mortality of the procedure, and the significant morbidity due to lifelong immunosuppression. A significant advancement that has led to the development of tissue engineered whole organs is the recellularization of xenogeneic or allogeneic decellularized matrices. A variety of different patient-specific stem cell sources maybe well suited to recellularize these matrices and translate to a clinical model. These matrices provide natural extracellular matrix (ECM) proteins and allow for cellular interaction and anchoring in three dimensions. Our lab is currently using physiologic isolated heart & lung bioreactors to generate decellularized and non-immunogenic scaffolds that can be repopulated using the patient specific cells mentioned previously. Our lab is also working to implant these engineer scaffolds in vivo to assess for their ability to perform important physiologic functions such as gas exchange.

Given our expertise in stem cell techniques, the opportunity to evaluate pediatric cancer stem cells arose. Currently we are investigating the feasibility of isolating neuroblastoma cancer stem cells from pediatric patients. Neuroblastoma is the most common extracranial solid cancer in childhood with an annual incidence of 650 cases per year in the United States. It arises from the neural crest and advanced disease can be associated with a poor prognosis.

The ability to isolate the aggressive stem cells from these tumors may give us unique information about the biology of the tumor and enhance the ability to find appropriate drug treatments.

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Current Research Projects

Human Patient Specific Stem Cells

  • Isolation and reprogramming of human fibroblasts using a excisable reprogramming lentiviral cassette
  • Differentiation of human iPSC and Embryonic Stem (ES) cells to distal airway type cells using small molecules and growth factors
  • Isolation and characterization of amniotic fluid stem cells from discarded amniocentesis samples
  • Reprogramming and differentiation of human amniotic fluid stem cells into distal airway type cells

Generation of Decellularized Lung Scaffolds

  • Rapid production of decellularized matrix using pressure-based or flow-based perfusion through the vasculature
  • Evaluation of protein content following the decellularization process
  • Production of a sterile matrix that can be further reseeded and cultured in vitro

Recellularization of Decellularized Lung Scaffolds

  • Optimizing the number of cells needed to appropriately reseed a lung scaffold
  • Use of patient-specific stem cells to repopulate the airways of lung scaffolds
  • Use of patient specific stem cells and endothelial cells to repopulate the vasculature of lung scaffolds
  • Implantation of reseeded scaffolds in vivo to assess feasibility and physiologic function

Other Additional Projects

Generation of Engineered Esophagus

  • Production of a decellularized sterile matrix that can be further reseeded and cultured in vitro
  • Reseeding the scaffold with patient specific stem cells with or without the use of differentiation protocols
  • Implantation of the scaffold to assess feasibility and physiologic function

Isolation of Cancer Stem Cells from Neuroblastoma

  • Digestion and characterization of neuroblastoma samples obtained from Connecticut Children’s Medical Center surgery department
  • Isolation and characterization of CD133+ cancer stem-like cells
  • In vivo studies to investigate the metastatic abilities and differences in tumorgenesis of CD133- and CD133+ cells
  • Investigate treatments specific to CD133+ cancer stem-like cells

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Publications

Jensen T, Roszell B, Zang F, Girard E, Matson A, Thrall R, Jaworski DM, Hatton C, Weiss DJ, Finck C. A rapid lung de-cellularization protocol supports embryonic stem cell differentiation in vitro and following implantation. Tissue Eng Part C Methods. 2012 Aug;18(8):632-46. Epub 2012 Apr 17. PubMed PMID: 22404373; PubMed Central PMCID: PMC3401389.

Weiss DJ, Finck C. Embryonic stem cells and repair of lung injury. Mol Ther. 2010 Mar;18(3):460-1. PubMed PMID: 20195263; PubMed Central PMCID: PMC2839420.

Roszell B, Mondrinos MJ, Seaton A, Simons DM, Koutzaki SH, Fong GH, Lelkes PI, Finck CM. Efficient derivation of alveolar type II cells from embryonic stem cells for in vivo application. Tissue Eng Part A. 2009 Nov;15(11):3351-65. PubMed PMID: 19388834; PubMed Central PMCID: PMC2811058.

Roszell B, Seaton A, Fong GH, Finck CM. Cell-based therapy improves cell viability and increases airway size in an explant model. Exp Lung Res. 2009 Aug;35(6):501-13. PubMed PMID: 19842834.

Mondrinos MJ, Koutzaki SH, Poblete HM, Crisanti MC, Lelkes PI, Finck CM. In vivo pulmonary tissue engineering: contribution of donor-derived endothelial cells to construct vascularization. Tissue Eng Part A. 2008 Mar;14(3):361-8. PubMed PMID: 18333788.

Mondrinos MJ, Koutzaki S, Lelkes PI, Finck CM. A tissue-engineered model of fetal distal lung tissue. Am J Physiol Lung Cell Mol Physiol. 2007 Sep;293(3):L639-50. Epub 2007 May 25. PubMed PMID: 17526596.

Mondrinos MJ, Koutzaki S, Jiwanmall E, Li M, Dechadarevian JP, Lelkes PI, Finck CM. Engineering three-dimensional pulmonary tissue constructs. Tissue Eng. 2006 Apr;12(4):717-28. PubMed PMID: 16674286.

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