scholarly journals Human Hemangioblast-Derived Mesenchymal Stem Cells Promote Islet Engraftment in a Minimal Islet Mass Transplantation Model in Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Suzanne Bertera ◽  
Michael F. Knoll ◽  
Carmela Knoll ◽  
Hidetaka Hara ◽  
Erin A. Kimbrel ◽  
...  

Islet transplantation can restore glycemic control in patients with type 1 diabetes. Using this procedure, the early stages of engraftment are often crucial to long-term islet function, and outcomes are not always successful. Numerous studies have shown that mesenchymal stem cells (MSCs) facilitate islet graft function. However, experimental data can be inconsistent due to variables associated with MSC generation (including donor characteristics and tissue source), thus, demonstrating the need for a well-characterized and uniform cell product before translation to the clinic. Unlike bone marrow- or adipose tissue-derived MSCs, human embryonic stem cell-derived-MSCs (hESC-MSCs) offer an unlimited source of stable and highly-characterized cells that are easily scalable. Here, we studied the effects of human hemangioblast-derived mesenchymal cells (HMCs), (i.e., MSCs differentiated from hESCs using a hemangioblast intermediate), on islet cell transplantation using a minimal islet mass model. The co-transplantation of the HMCs allowed a mass of islets that was insufficient to correct diabetes on its own to restore glycemic control in all recipients. Our in vitro studies help to elucidate the mechanisms including reduction of cytokine stress by which the HMCs support islet graft protection in vivo. Derivation, stability, and scalability of the HMC source may offer unique advantages for clinical applications, including fewer islets needed for successful islet transplantation.

2016 ◽  
Vol 2016 ◽  
pp. 1-22 ◽  
Author(s):  
Nadine E. Rekittke ◽  
Meidjie Ang ◽  
Divya Rawat ◽  
Rahul Khatri ◽  
Thomas Linn

Type 1 diabetes is an autoimmune disease resulting in the permanent destruction of pancreatic islets. Islet transplantation to portal vein provides an approach to compensate for loss of insulin producing cells. Clinical trials demonstrated that even partial islet graft function reduces severe hypoglycemic events in patients. However, therapeutic impact is restrained due to shortage of pancreas organ donors and instant inflammation occurring in the hepatic environment of the graft. We summarize on what is known about regenerative therapy in type 1 diabetes focusing on pancreatic islet transplantation and new avenues of cell substitution. Metabolic pathways and energy production of transplanted cells are required to be balanced and protection from inflammation in their intravascular bed is desired. Mesenchymal stem cells (MSCs) have anti-inflammatory features, and so they are interesting as a therapy for type 1 diabetes. Recently, they were reported to reduce hyperglycemia in diabetic rodents, and they were even discussed as being turned into endodermal or pancreatic progenitor cells. MSCs are recognized to meet the demand of an individual therapy not raising the concerns of embryonic or induced pluripotent stem cells for therapy.


2010 ◽  
Vol 12 (6) ◽  
pp. 435-446 ◽  
Author(s):  
Biancamaria Longoni ◽  
Erzsebet Szilagyi ◽  
Paola Quaranta ◽  
Giacomo Timoteo Paoli ◽  
Sergio Tripodi ◽  
...  

2020 ◽  
pp. 1-3
Author(s):  
Rim M Harfouch ◽  
◽  
Hrag Torossian ◽  
Hala Qabalan ◽  
◽  
...  

Islet cell transplantation has therapeutic potential to treat type 1 diabetes, which is characterized by autoimmune destruction of insulin-producing pancreatic islet β cells. It represents a minimal invasive approach for β cell replacement, but long-term blood control is still largely unachievable. This phenomenon can be attributed to the lack of islet vasculature and hypoxic environment in the immediate post-transplantation period that contributes to the acute loss of islets by ischemia. Moreover, graft failures continue to occur because of immunological rejection, despite the use of potent immunosuppressive agents. Mesenchymal stem cells (MSCs) have the potential to enhance islet transplantation by suppressing inflammatory damage and immune mediated rejection. In this review we discuss the impact of MSCs on islet transplantation and focus on the potential role of MSCs in protecting islet grafts from early graft failure and from autoimmune attack.


2009 ◽  
Vol 41 (5) ◽  
pp. 1797-1800 ◽  
Author(s):  
M. Figliuzzi ◽  
R. Cornolti ◽  
N. Perico ◽  
C. Rota ◽  
M. Morigi ◽  
...  

2010 ◽  
Vol 5 (3) ◽  
pp. 180-190 ◽  
Author(s):  
Sanne K. Both ◽  
Aart A. van Apeldoorn ◽  
Jojanneke M. Jukes ◽  
Mikael C.O. Englund ◽  
Johan Hyllner ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-18 ◽  
Author(s):  
Chad M. Teven ◽  
Xing Liu ◽  
Ning Hu ◽  
Ni Tang ◽  
Stephanie H. Kim ◽  
...  

Stem cells are characterized by their capability to self-renew and terminally differentiate into multiple cell types. Somatic or adult stem cells have a finite self-renewal capacity and are lineage-restricted. The use of adult stem cells for therapeutic purposes has been a topic of recent interest given the ethical considerations associated with embryonic stem (ES) cells. Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Owing to their ease of isolation and unique characteristics, MSCs have been widely regarded as potential candidates for tissue engineering and repair. While various signaling molecules important to MSC differentiation have been identified, our complete understanding of this process is lacking. Recent investigations focused on the role of epigenetic regulation in lineage-specific differentiation of MSCs have shown that unique patterns of DNA methylation and histone modifications play an important role in the induction of MSC differentiation toward specific lineages. Nevertheless, MSC epigenetic profiles reflect a more restricted differentiation potential as compared to ES cells. Here we review the effect of epigenetic modifications on MSC multipotency and differentiation, with a focus on osteogenic and adipogenic differentiation. We also highlight clinical applications of MSC epigenetics and nuclear reprogramming.


2018 ◽  
Vol 2 (1) ◽  

The research on nitric Oxide (NO) and stem cells are the focus in recent years. However, seldom do people conclude the function, mechanism and clinical value of NO in various stem cells including embryonic stem cells (ESCs), endothelial progenitor cells (EPCs), mesenchymal stem cells (MSCs) and neural stem cells (NSCs). In the present review, we evaluate the recent studies on NO in different stem cells and display the latest progresses of NO therapy for tumor, cardiovascular, neurologic and immune system diseases by stem cells.


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