Corinne A Hoesli

• Ph.D.
• Professor (Associate) at McGill University

Islet transplantation and more recently stem cell-derived islets were shown to successfully re-establish glycemic control in people with type 1 diabetes under immunosuppression. These results were achieved through intraportal infusion which leads to early graft losses and limits the capacity to contain and retrieve implanted cells in case of advers...

Despite their recognized potential for ischemic tissue repair, the clinical use of human mesenchymal stromal cells (hMSC) is limited by the poor viability of cells after injection and the variability of their paracrine function. In this study, we show how the choice of biomaterial scaffolds and the addition of cell preconditioning treatment can add...

Several emerging strategies to engineer artificial organs employ 3D printing to create vascular templates to provide nutrients and oxygen to immobilized cells. Many systems also require efficient counter-diffusion of therapeutic molecules, as is the case for bioartificial pancreas strategies. Significant challenges emerge when considering clinical...

Hydrogels are commonly used to immobilize mammalian cells, serving various purposes such as providing mechanical cues in three-dimensional cultures and acting as barriers for immunoprotection in transplantation. For instance, islet encapsulation holds promise in delivering insulin-producing cells for diabetes cellular therapy. Cell immobilization,...

β-Cell replacement for type 1 diabetes (T1D) can restore normal glucose homeostasis, thereby eliminating the need for exogenous insulin and halting the progression of diabetes complications. Success in achieving insulin independence following transplantation of cadaveric islets fueled academic and industry efforts to develop techniques to mass prod...

Type 1 diabetes (T1D) is an autoimmune disease that leads to the loss of insulin-producing beta cells. Bioartificial pancreas (BAP) or beta cell replacement strategies have shown promise in curing T1D and providing long-term insulin independence. Hypoxia (low oxygen concentration) that may occur in the BAP devices due to cell oxygen consumption at...

Microchannel emulsification can produce droplets of uniform size at high throughput for wide-ranging applications in the food and drug industry. Mammalian cell encapsulation using emulsion-based systems is of significant interest for immobilized culture or transplantation applications. Microchannel emulsification has recently been applied to mammal...

Maximizing the re-endothelialization of vascular implants such as prostheses or stents has the potential to significantly improve their long-term performance. Endothelial progenitor cell capture stents with surface-immobilized antibodies show significantly improved endothelialization in the clinic. However, most current antibody-based stent surface...

Mesenchymal stromal/stem cells hold potential in repairing damaged tissue through paracrine effects. Their delivery though injectable biodegradable microbeads can improve cell retention and survival at the infusion site. A stirred emulsion process was previously implemented to immobilize these cells in injectable chitosan microbeads for cell therap...

A prominent obstacle in scaling up tissue engineering technologies for human applications is engineering an adequate supply of oxygen and nutrients throughout artificial tissues. Sugar glass has emerged as a promising 3D-printable, sacrificial material that can be used to embed perfusable networks within cell-laden matrices to improve mass transfer...

In Cell Stem Cell, Aghazadeh et al.¹ • Aghazadeh Y. • Poon F. • Sarangi F. • Wong F.T.M. • Khan S.T. • Sun X. • Hatkar R. • Cox B.J. • Nunes S.S. • Nostro M.C. Microvessels support engraftment and functionality of human islets and hESC-derived pancreatic progenitors in diabetes models.Cell Stem Cell. 2021; (S1934-5909(21)00338-6)https://doi.org/10...

Maximizing the re-endothelialization of vascular implants such as prostheses or stents has the potential to significantly improve their long-term performance. Endothelial progenitor cell capture stents with surface-immobilized antibodies show significantly improved endothelialization in the clinic. However, most current antibody-based stent surface...

Transplantation of hydrogel-encapsulated pancreatic islets is a promising long-term treatment for type 1 diabetes that restores blood glucose regulation while providing graft immunoprotection. Most human-scale islet encapsulation devices that rely solely on diffusion fail to provide sufficient surface area to meet islet oxygen demands. Perfused mac...

Micropatterned cell cultures provide an important tool to understand dynamic biological processes, but often require specialized equipment and expertise. Here we present subtractive bioscribing (SuBscribe), a readily accessible and inexpensive technique to generate dynamic micropatterns in biomaterial monolayers on-the-fly. We first describe our mo...

Different bioinks have been used to produce cell-laden alginate-based hydrogel constructs for cell replacement therapy but some of these approaches suffer from issues with print quality, long-term mechanical instability, and bioincompatibility. In this study, new alginate-based bioinks were developed to produce cell-laden grid-shaped hydrogel const...

Background: A major obstacle to anti-viral and -tumor cell vaccination and T cell immunotherapy is the ability to produce dendritic cells (DCs) in a suitable clinical setting. It is imperative to develop closed cell culture systems to accelerate the translation of promising DC-based cell therapy products to the clinic. The objective of this study...

Insulin-producing beta cells sourced from pluripotent stem cells hold great potential as a virtually unlimited cell source to treat diabetes. Directed pancreatic differentiation protocols aim to mimic various stimuli present during embryonic development through sequential changes of in vitro culture conditions. This is commonly accomplished by the...

Antibody surface immobilization is a promising strategy to capture cells of interest from circulating fluids in vitro and in vivo. An application of particular interest in vascular interventions is to capture endothelial progenitor cells (EPCs) on the surface of stents to accelerate endothelialization. The clinical impact of EPC capture stents has...

Today's Biochemical Engineer may contribute to advances in a wide range of technical areas. The recent Biochemical and Molecular Engineering XXI conference focused on “The Next Generation of Biochemical and Molecular Engineering: The role of emerging technologies in tomorrow's products and processes”. On the basis of topical discussions at this con...

Background & Aim Modern cell based therapies continue to gain momentum as demonstrated by the growing number of clinical trials and cell therapy commercialization centers. A growing shift towards closed manufacturing systems to replace conventional functionally open systems such as tissue culture polystyrene (TCPS) flasks has prompted the developme...

The use of polylactic acid (PLA) has attracted growing interest, particularly in recent years, for biomedical applications because of its mechanical properties, biocompatibility, and biodegradability. Despite this, features such as surface hydrophobicity and the absence of suitable functional groups for covalent immobilization of bioactive molecule...

Pluripotent stem cell (PSC)-derived insulin-producing cells are a promising cell source for diabetes cellular therapy. However, the efficiency of the multi-step process required to differentiate PSCs towards pancreatic beta cells is variable between cell lines, batches and even within cultures. In adherent pancreatic differentiation protocols, we o...

Cell microencapsulation is a promising approach to improve cell therapy outcomes, by protecting injected cells from rapid dispersion and allowing bidirectional diffusion of nutrients, oxygen and waste that promote cell survival in the target tissues. Here, we describe a simple and scalable emulsification method to encapsulate animal cells in chitos...

Pure pancreatic β cells play a major role in multiple areas of diabetic research, nevertheless, the separation of β cells remains a challenge. The objective of this study is to show the feasibility of using plasma polymers to remove fibroblasts from β cells. Oxygen‐ and nitrogen‐rich organic coatings with different O and N concentrations were prepa...

Conventional cell culture surfaces typically consist of polystyrene, with or without surface modifications created through plasma treatment or protein/peptide coating strategies. Other polymers such as fluorinated ethylene propylene are increasingly being implemented in the design of closed cell culture vessels, for example to facilitate the produc...

The expansion of human peripheral blood endothelial progenitor cells to obtain therapeutically relevant endothelial colony‐forming cells (ECFCs) has been commonly performed on xeno‐derived extracellular matrix proteins. For cellular therapy applications, xeno‐free culture conditions are desirable to improve product safety and reduce process variabi...

The expansion of human peripheral blood endothelial progenitor cells to obtain therapeutically relevant endothelial colony forming cells (ECFCs) has been commonly performed on xeno‐derived extracellular matrix proteins. For cellular therapy applications, xeno‐free culture conditions are desirable to improve product safety and reduce process variabi...

In this study, we developed a high‐throughput microchannel emulsification process to encapsulate pancreatic beta cells in monodisperse alginate beads. The process builds on a stirred emulsification and internal gelation method previously adapted to pancreatic cell encapsulation. Alginate bead production was achieved by flowing a 0.5–2.5% alginate s...

Type 1 diabetes (T1D) is an autoimmune condition in which insulin-producing, pancreatic Β-cells are destroyed by the immune system. Islet transplantation presents a potential long-term cell therapy for T1D however, the efficacy, safety, and availability of this treatment option is limited. This work presents an overview of cell encapsulation as a c...

Surface endothelialization could improve the long-term performance of vascular grafts and stents. We previously demonstrated that aerosol-generated fibronectin-derived peptide micropatterns consisting of GRGDS spots over a WQPPRARI background increased endothelial cell yields in static cultures. We developed a novel fluorophore-tagged RGD peptide (...

The interactions between monocytes and biomaterials can potentially be modulated by controlling the chemical and structural surface properties of biomaterials. The objective of this study was to determine the effect of plasma-deposited functional organic coatings on monocyte adhesion and differentiation into macrophages. Organic coatings with varyi...

Microencapsulation is being investigated as a means to avoid rejection of transplanted pancreatic islets. Monitoring bead distribution and stability in vivo is an important step towards improving microencapsulated islet transplantation strategies. Islet co-encapsulation with gadolinium-labeled mesoporous silica nanoparticles (Gd-MSNs) could provide...

Delayed endothelialization of vascular prosthesis after percutaneous coronary intervention increases the risk of in-stent thrombosis and restenosis, decreasing the long term patency of the implants. In this study, we investigated the ability of a novel peptide, RGD-TAMRA, in inducing the adhesion and expansion of endothelial progenitor cells (EPCs)...

In recent years, cell‐based therapies targeting the immune system have emerged as promising strategies for cancer treatment. This review summarizes manufacturing challenges related to production of antigen presenting cells as a patient‐tailored cancer therapy. Understanding cell‐material interactions is essential because in vitro cell culture manip...

Cell encapsulation in alginate beads has been used for immobilized cell culture in vitro as well as for immunoisolation in vivo. Pancreatic islet encapsulation has been studied extensively as a means to increase islet survival in allogeneic or xenogeneic transplants. Alginate encapsulation is commonly achieved by nozzle extrusion and external gelat...

Additive manufacturing is now considered as a new paradigm that is foreseen to improve progress in many fields. The field of tissue engineering has been facing the need for tissue vascularization when producing thick tissues. The use of sugar glass as a fugitive ink to produce vascular networks through rapid casting may offer the key to vasculariza...

Induced pluripotent stem cells (iPSCs) have opened new doors in providing an ethical, patient-specific cell source towards tissue engineering. Developing these therapies involves the production of reprogrammed iPSCs, expanding them while maintaining pluripotency, then differentiating them into functional tissues. To bring these therapies to the cli...

Ethyl lactate is injected into a dielectric barrier discharge (DBD) to build up a degradable plasma polymer (PP) to be used as a drug delivery system. Plasma power, deposition time, and type of carrier gas (Ar, N2) are correlated to the coating in vitro degradation rate. PPs are characterized by AFM, SEM, IR spectroscopy, XPS, and SEC, while surfac...

In recent years, cell-based therapies targeting the immune system have emerged as promising strategies for cancer treatment. This review summarizes manufacturing challenges related to production of antigen presenting cells as a patient-tailored cancer therapy. Understanding cell-material interactions is essential because in vitro cell culture manip...

* Correspondence: Dr. Morgane Laurent, Université de Toulouse - CNRS, LAPLACE, Toulouse, France, Email1 Dr. Julia Köhler, Université de Toulouse - CNRS, LAPLACE, Toulouse, France, Email2 Dr. Gad Sabbatier, Université Laval, Dep. of Materials Engineering, Québec, QC, Canada, Email3 Dr. Corinne Hoesli, Université Laval, Dep. of Materials Engineering,...

Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder caused by a de novo genetic mutation that leads to the accumulation of a splicing isoform of lamin A termed progerin. Progerin expression alters the organization of the nuclear lamina and chromatin. The life expectancy of HGPS patients is severely reduced due to critical card...

Since thirty years, efforts were put forward to engineer materials that could be used to build up biomedical devices that have to come in contact with human tissues. The first devices that were developed were designed to reproduce the basic functions of the tissue or organ that they were intended to replace. For example, the first designs of arteri...

Background Pancreatic adenocarcinoma is one of the most lethal cancers, yet it remains understudied and poorly understood. Hyperinsulinemia has been reported to be a risk factor of pancreatic cancer, and the rapid rise of hyperinsulinemia associated with obesity and type 2 diabetes foreshadows a rise in cancer incidence. However, the actions of ins...

Intimal hyperplasia and thrombosis are responsible for the poor patency rates of small-diameter vascular grafts. These complications could be avoided by a rapid and strong adhesion of endothelial cells to the prosthetic surfaces, which typically consist of expanded polytetrafluoroethylene (PTFE) for small-diameter vessels. We have previously descri...

Encapsulation of insulin-producing cells in alginate beads could improve the treatment of type 1 diabetes by reducing or eliminating the need for immunosuppression. We have recently adapted an emulsion and internal gelation process to β-cell encapsulation. This process has the advantages of being well suited for m(3)/h production rates and allowing...

The proliferation of pancreatic duct-like CK19+ cells has implications for multiple disease states including pancreatic cancer and diabetes mellitus. The in vitro study of this important cell type has been hampered by their limited expansion compared to fibroblast-like vimentin+ cells that overgrow primary cultures. We aimed to develop a screening...

Dataset S1 in comma-separated values format. (TXT)

Dataset used to compute the 25 full factorial effects of reported duct mitogens on CK19+ cell proliferation (Figure 5). This dataset provides the cell number, the fraction of cells expressing CK19, the fraction of cells that did not express vimentin, as well as the BrdU incorporation by the CK19+ or vimentin− cells. The data are also provided as va...

Achieving high-level expansion of hematopoietic stem cells (HSCs) in vitro will have an important clinical impact in addition to enabling elucidation of their regulation. Here, we couple the ability of engineered NUP98-HOXA10hd expression to stimulate > 1000-fold net expansions of murine HSCs in 10-day cultures initiated with bulk lin(-)Sca-1(+)c-k...

Alginate has been used to protect transplanted pancreatic islets from immune rejection and as a matrix to increase the insulin content of islet progenitor cells. The throughput of alginate bead generation by the standard extrusion and external gelation method is limited by the rate of droplet formation from nozzles. Alginate bead generation by emul...

Object identification and segmentation. Example images of Hoechst-treated human pancreatic tissue (A, B, C) and MIN6 cells (D, E, F) acquired by the Cellomics ArrayScan VI. Raw images (A, D) were subjected to the Cellomics Target Activation BioApplication's nuclear identification (B, E) and cytoplasmic masking (C, F). Blue indicates objects that ar...

Example row and column biases in 96-well format high-throughput data. Examples of row (A, B) and column (C, D) effects in Hoechst expression of human pancreatic tissue (A, C) and in cell number in MIN6 (B, D) data of individual plates. Row and column effects are generally more pronounced in the human data. Lower expression levels in the perimeter w...

Effect of glucose on insulin promoter activity. (A) Control experiments with 5 mM glucose and 10 mM glucose demonstrating the magnitude of effects on insulin promoter activity under physiological conditions. Asterisks denote significant difference from DMSO control (n = 3). (B) Representative traces of Fura-2 loaded MIN6 cells exposed to 10 mM gluc...

Real-time PCR analysis of Insulin and Pdx1 mRNA in MIN6 cells treated with Hit #3 crude extract. Effects of butanol extract and crude extract of hit #3, a sea cucumber echinoderm from Pohnpei (Original sample number# 47583 in the library). Asterisks denote significant difference from DMSO control (n = 4 for all experiments). (0.12 MB PDF)

Supplemental Methods. (0.09 MB DOC)

High-throughput, high-content experimental design. Shown are the timelines for both MIN6 cell experiments and experiments performed on dispersed human islets cells. (0.05 MB PDF)

B score transformation corrects row and column biases in individual plates. Row (A, B) and column (C, D) effects in Hoechst expression of human pancreatic tissue (A, C) and in cell number in MIN6 (B, D) data after B score transformation. These data correspond to the data in Figure S3. (0.08 MB PDF)

B score transformed data compared with raw data. Correlations between median values per well (X-axis) and B-score transformed values per well (Y-axis) for each extract for each of the 4 parameters analyzed. (0.14 MB PDF)

Effect of purified fractions from hit #3 and Holothurin A on insulin secretion in MIN6 cells. MIN6 cells were treated for 18 hours in DMEM 22.5 mM glucose containing media supplemented with 10% FBS and 0.2 to 2000 ng/mL purified sponge library extract #47583:BuOH-A (A), #47583:BuOH-B (B), #47583:BuOH-C (C), or Holothurin A (D). Media were collected...

Effect of crude extract of hit # 2 on insulin secretion from MIN6 cells. MIN6 cells were treated for 24 hours in serum free media supplemented with 1∶1, 1∶10, 1∶100, 1∶1000 dilutions of the hit #2 sponge extract (original library number #03-436). Media was collected and insulin levels were assayed with rat insulin RIA kit. n = 5, mean ± SEM. (0.07...

Correlation of MIN6 data with a single multi-parameter high content screen on human islet cell cultures. B scores are shown for a subset of the data illustrated in Figure 3 and a corresponding data set compiled from human islet cells exposed to the same extracts. Correlations are shown. (0.23 MB PDF)

Effects of purified fractions from hit #2 on Insulin and Pdx1 promoter activity in MIN6 cells. Insulin promoter activity (green), Pdx1 promoter activity (red), and total cell number (purple) was analyzed for 5 doses of crude, butanol, aqueous extracts of hit #2, as well as four ethanol purified fractions from this extract (A–D). (0.14 MB PDF)

Diabetes is a devastating disease that is ultimately caused by the malfunction or loss of insulin-producing pancreatic beta-cells. Drugs capable of inducing the development of new beta-cells or improving the function or survival of existing beta-cells could conceivably cure this disease. We report a novel high-throughput screening platform that exp...

Gel-matrix culture environments provide tissue engineering scaffolds and cues that guide cell differentiation. For many cellular therapy applications such as for the production of islet-like clusters to treat Type 1 diabetes, the need for large-scale production can be anticipated. The throughput of the commonly used nozzle-based devices for cell en...