Christine Finck, M.D.
Center for Vascular Biology
University of Connecticut Health Center
263 Farmington Avenue
Farmington, CT 06030-3501
Christine Finck, M.D.
Stephanie Vadasz, Ph.D.
Todd Jensen, M.S.
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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
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
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
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
- Differentiation of human iPSC and
Embryonic Stem (ES) cells to distal airway
type cells using small molecules and growth
- Isolation and characterization of
amniotic fluid stem cells from discarded
- 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
- 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
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
- 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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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
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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