Tyler Allen

Positions:

Postdoctoral Associate

Duke Cancer Institute
School of Medicine

Grants:

Publications:

Derivation of therapeutic lung spheroid cells from minimally invasive transbronchial pulmonary biopsies.

<h4>Background</h4>Resident stem and progenitor cells have been identified in the lung over the last decade, but isolation and culture of these cells remains a challenge. Thus, although these lung stem and progenitor cells provide an ideal source for stem-cell based therapy, mesenchymal stem cells (MSCs) remain the most popular cell therapy product for the treatment of lung diseases. Surgical lung biopsies can be the tissue source but such procedures carry a high risk of mortality.<h4>Methods</h4>In this study we demonstrate that therapeutic lung cells, termed "lung spheroid cells" (LSCs) can be generated from minimally invasive transbronchial lung biopsies using a three-dimensional culture technique. The cells were then characterized by flow cytometry and immunohistochemistry. Angiogenic potential was tested by in-vitro HUVEC tube formation assay. In-vivo bio- distribution of LSCs was examined in athymic nude mice after intravenous delivery.<h4>Results</h4>From one lung biopsy, we are able to derive >50 million LSC cells at Passage 2. These cells were characterized by flow cytometry and immunohistochemistry and were shown to represent a mixture of lung stem cells and supporting cells. When introduced systemically into nude mice, LSCs were retained primarily in the lungs for up to 21 days.<h4>Conclusion</h4>Here, for the first time, we demonstrated that direct culture and expansion of human lung progenitor cells from pulmonary tissues, acquired through a minimally invasive biopsy, is possible and straightforward with a three-dimensional culture technique. These cells could be utilized in long-term expansion of lung progenitor cells and as part of the development of cell-based therapies for the treatment of lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).
Authors
Dinh, P-UC; Cores, J; Hensley, MT; Vandergriff, AC; Tang, J; Allen, TA; Caranasos, TG; Adler, KB; Lobo, LJ; Cheng, K
MLA Citation
Dinh, Phuong-Uyen C., et al. “Derivation of therapeutic lung spheroid cells from minimally invasive transbronchial pulmonary biopsies.Respiratory Research, vol. 18, no. 1, June 2017, p. 132. Epmc, doi:10.1186/s12931-017-0611-0.
URI
https://scholars.duke.edu/individual/pub1471595
PMID
28666430
Source
epmc
Published In
Respiratory Research
Volume
18
Published Date
Start Page
132
DOI
10.1186/s12931-017-0611-0

A Regenerative Cardiac Patch Formed by Spray Painting of Biomaterials onto the Heart.

Layering a regenerative polymer scaffold on the surface of the heart, termed as a cardiac patch, has been proven to be effective in preserving cardiac function after myocardial infarction (MI). However, the placement of such a patch on the heart usually needs open-chest surgery, which is traumatic, therefore prevents the translation of this strategy into the clinic. We sought to device a way to apply a cardiac patch by spray painting in situ polymerizable biomaterials onto the heart with a minimally invasive procedure. To prove the concept, we used platelet fibrin gel as the "paint" material in a mouse model of MI. The use of the spraying system allowed for placement of a uniform cardiac patch on the heart in a mini-invasive manner without the need for sutures or glue. The spray treatment promoted cardiac repair and attenuated cardiac dysfunction after MI.
Authors
Tang, J; Vandergriff, A; Wang, Z; Hensley, MT; Cores, J; Allen, TA; Dinh, P-U; Zhang, J; Caranasos, TG; Cheng, K
MLA Citation
Tang, Junnan, et al. “A Regenerative Cardiac Patch Formed by Spray Painting of Biomaterials onto the Heart.Tissue Engineering. Part C, Methods, vol. 23, no. 3, Mar. 2017, pp. 146–55. Epmc, doi:10.1089/ten.tec.2016.0492.
URI
https://scholars.duke.edu/individual/pub1471594
PMID
28068869
Source
epmc
Published In
Tissue Engineering. Part C, Methods
Volume
23
Published Date
Start Page
146
End Page
155
DOI
10.1089/ten.tec.2016.0492

Therapeutic microparticles functionalized with biomimetic cardiac stem cell membranes and secretome.

Stem cell therapy represents a promising strategy in regenerative medicine. However, cells need to be carefully preserved and processed before usage. In addition, cell transplantation carries immunogenicity and/or tumourigenicity risks. Mounting lines of evidence indicate that stem cells exert their beneficial effects mainly through secretion (of regenerative factors) and membrane-based cell-cell interaction with the injured cells. Here, we fabricate a synthetic cell-mimicking microparticle (CMMP) that recapitulates stem cell functions in tissue repair. CMMPs carry similar secreted proteins and membranes as genuine cardiac stem cells do. In a mouse model of myocardial infarction, injection of CMMPs leads to the preservation of viable myocardium and augmentation of cardiac functions similar to cardiac stem cell therapy. CMMPs (derived from human cells) do not stimulate T-cell infiltration in immuno-competent mice. In conclusion, CMMPs act as 'synthetic stem cells' which mimic the paracrine and biointerfacing activities of natural stem cells in therapeutic cardiac regeneration.
Authors
Tang, J; Shen, D; Caranasos, TG; Wang, Z; Vandergriff, AC; Allen, TA; Hensley, MT; Dinh, P-U; Cores, J; Li, T-S; Zhang, J; Kan, Q; Cheng, K
MLA Citation
Tang, Junnan, et al. “Therapeutic microparticles functionalized with biomimetic cardiac stem cell membranes and secretome.Nature Communications, vol. 8, Jan. 2017, p. 13724. Epmc, doi:10.1038/ncomms13724.
URI
https://scholars.duke.edu/individual/pub1471599
PMID
28045024
Source
epmc
Published In
Nature Communications
Volume
8
Published Date
Start Page
13724
DOI
10.1038/ncomms13724

Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis.

<h4>Unlabelled</h4>Lung diseases are devastating conditions and ranked as one of the top five causes of mortality worldwide according to the World Health Organization. Stem cell therapy is a promising strategy for lung regeneration. Previous animal and clinical studies have focused on the use of mesenchymal stem cells (from other parts of the body) for lung regenerative therapies. We report a rapid and robust method to generate therapeutic resident lung progenitors from adult lung tissues. Outgrowth cells from healthy lung tissue explants are self-aggregated into three-dimensional lung spheroids in a suspension culture. Without antigenic sorting, the lung spheroids recapitulate the stem cell niche and contain a natural mixture of lung stem cells and supporting cells. In vitro, lung spheroid cells can be expanded to a large quantity and can form alveoli-like structures and acquire mature lung epithelial phenotypes. In severe combined immunodeficiency mice with bleomycin-induced pulmonary fibrosis, intravenous injection of human lung spheroid cells inhibited apoptosis, fibrosis, and infiltration but promoted angiogenesis. In a syngeneic rat model of pulmonary fibrosis, lung spheroid cells outperformed adipose-derived mesenchymal stem cells in reducing fibrotic thickening and infiltration. Previously, lung spheroid cells (the spheroid model) had only been used to study lung cancer cells. Our data suggest that lung spheroids and lung spheroid cells from healthy lung tissues are excellent sources of regenerative lung cells for therapeutic lung regeneration.<h4>Significance</h4>The results from the present study will lead to future human clinical trials using lung stem cell therapies to treat various incurable lung diseases, including pulmonary fibrosis. The data presented here also provide fundamental knowledge regarding how injected stem cells mediate lung repair in pulmonary fibrosis.
Authors
Henry, E; Cores, J; Hensley, MT; Anthony, S; Vandergriff, A; de Andrade, JBM; Allen, T; Caranasos, TG; Lobo, LJ; Cheng, K
MLA Citation
Henry, Eric, et al. “Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis.Stem Cells Translational Medicine, vol. 4, no. 11, Nov. 2015, pp. 1265–74. Epmc, doi:10.5966/sctm.2015-0062.
URI
https://scholars.duke.edu/individual/pub1471596
PMID
26359426
Source
epmc
Published In
Stem Cells Translational Medicine
Volume
4
Published Date
Start Page
1265
End Page
1274
DOI
10.5966/sctm.2015-0062

Rapid and Efficient Production of Coronary Artery Ligation and Myocardial Infarction in Mice Using Surgical Clips.

<h4>Aims</h4>The coronary artery ligation model in rodents mimics human myocardial infarction (MI). Normally mechanical ventilation and prolonged anesthesia period are needed. Recently, a method has been developed to create MI by popping-out the heart (without ventilation) followed by immediate suture ligation. Mortality is high due to the time-consuming suture ligation process while the heart is exposed. We sought to improve this method and reduce mortality by rapid coronary ligation using a surgical clip instead of a suture.<h4>Methods and results</h4>Mice were randomized into 3 groups: clip MI (CMI), suture MI (SMI), or sham (SHAM). In all groups, heart was manually exposed without intubation through a small incision on the chest wall. Unlike the conventional SMI method, mice in the CMI group received a metal clip on left anterior descending artery (LAD), quickly dispensed by an AutoSuture Surgiclip™. The CMI method took only 1/3 of ligation time of the standard SMI method and improved post-MI survival rate. TTC staining and Masson's trichrome staining revealed a similar degree of infarct size in the SMI and CMI groups. Echocardiograph confirmed that both SMI and CMI groups had a similar reduction of ejection fraction and fraction shortening over the time. Histological analysis showed that the numbers of CD68+ macrophages and apoptotic cells (TUNEL-positive) are indistinguishable between the two groups.<h4>Conclusion</h4>This new method, taking only less than 3 minutes to complete, represents an efficient myocardial infarction model in rodents.
Authors
Andrade, JNBMD; Tang, J; Hensley, MT; Vandergriff, A; Cores, J; Henry, E; Allen, TA; Caranasos, TG; Wang, Z; Zhang, T; Zhang, J; Cheng, K
MLA Citation
Andrade, James NBM de, et al. “Rapid and Efficient Production of Coronary Artery Ligation and Myocardial Infarction in Mice Using Surgical Clips.Plos One, vol. 10, no. 11, Jan. 2015, p. e0143221. Epmc, doi:10.1371/journal.pone.0143221.
URI
https://scholars.duke.edu/individual/pub1471597
PMID
26599500
Source
epmc
Published In
Plos One
Volume
10
Published Date
Start Page
e0143221
DOI
10.1371/journal.pone.0143221

Research Areas:

Adult Stem Cells
Cancer
Cancer Disparities
Cell Biology
Mesenchymal stem cells
Metastasis
Stem Cells