• News
  • Spirituality
    • Dream Interpretation
    • Angel Numbers
    • Tarot
    • Prayers
    • Spells
  • Health
  • Science
  • Celebs
  • Betting

Type 1 Diabetes - Generating Pancreatic Β Cells From Mesenchymal Stem Cells For Treatment

144Shares
35.9KViews

Type 1 diabetes (T1D) is a long-term condition caused by an autoimmune attack on pancreatic cells. Hyperglycemia and its associated serious complications are caused by an insufficient supply of insulin. Islet cell transplantation has been investigated as a possible treatment for type 1 diabetes, as it provides new cells for blood glucose control.

However, because each patient requires two or four donor pancreases to receive effective cells, this approach is limited due to a lack of donors. As a result, new sources for transplantable islet cells should be investigated.

Several studies have successfully reversed hyperglycemia in animal models by transplanting ESC-derived cells in the laboratory. ESCs, on the other hand, are controversial as research materials, and their risk of tumorigenesis in vivo after transplantation restricts their clinical use.

More On Treating Type 1 Diabetes With Pancreatic Β Cells

Yamanaka et al. created induced pluripotent stem (iPS) cells from skin cells that can be redifferentiated to produce pancreatic cells, so iPS cells seemed like a promising source for cell production. But some risks exist with the use of iPS. The use of viruses in stem cell reprogramming has been linked to cancer, and the differentiation of iPS cells afterward has been linked to an increase in genetic mutations. This may predispose differentiated cell types to malignant transformation. Furthermore, teratoma formation may occur if differentiated cells contain undifferentiated iPS cells. As a result, a low-risk source that can differentiate into pancreatic cells should be thoroughly investigated.

COPYRIGHT_SZ: Published on https://stationzilla.com/type-1-diabetes/ by Alexander McCaslin on 2022-05-26T05:44:35.908Z

MSCs are a heterogeneous cell population with fibroblast-like morphology and the ability to differentiate into a variety of mesenchymal lineages cells, such as bone, fat, and cartilage, and they can proliferate in vitro on plastic culture flasks. MSCs can differentiate into neurons, hepatocytes, and endothelial cells, despite being mesoderm lineages. MSCs can also be isolated from almost any type of connective tissue and have the ability to differentiate into insulin-producing cells (IPCs) in vitro using a specific culture method.

A black woman wearing a green t-shirt with a white t-shirt using the blood sugar level machine needle on her finger
A black woman wearing a green t-shirt with a white t-shirt using the blood sugar level machine needle on her finger

Strategies To Generate Β Cells From MSCs

Friedenstein described MSCs as spindle-shaped and clonogenic cells in monolayer cultures when they were first isolated from bone marrow. In vitro and in vivo, they could transform into adipocytes, chondrocytes, and osteocytes. Further research revealed that multipotent stromal cells are the collective precursors of mesenchymal tissues, capable of differentiating into mesoderm, ectoderm, and endoderm cells. Caplan first defined these stromal cells, which existed in almost every type of connective tissue, as mesenchymal stem cells (MSC) because of their potential for differentiation and self-renewal. The ISCT Mesenchymal and Tissue Stem Cell Committee proposes a set of standards to define human MSC based on the best currently available data in order to provide specifications for pre-clinical and clinical studies.

MSC is defined by three standards:

  • Multipotent differentiation potential.
  • Specific surface antigen (Ag) expression.
  • Adherence to plastic

When maintained under standard culture conditions, MSC should adhere to the plastic surface of tissue culture flasks. Second, MSC must express CD105, CD73, and CD90, with a positive expression rate of 95% or greater. MSC is a heterogeneous population that lacks CD45, CD34, CD14, CD11b, CD79, CD19, or HLA-DR expression (2%), and will not be confused by other cells such as hematopoietic cells, endothelial cells, macrophages, or β-cells. Third, MSC can differentiate into osteoblasts, adipocytes, and chondroblasts in vitro.

MSCs Initiate Β Cell Regeneration

MSCs have been extensively studied in animal models and used to treat diabetes. Many animal studies revealed that transplanting MSCs into diabetic mice could lower blood glucose levels, increase weight, and extend their lifespan. Grafted stem cells have the ability to migrate into the injured pancreas and help it heal. Several chemokines and their receptors are linked to MSCs that have the ability to homing to injury sites. CXCR4, CX3CR1, CXCR6, CCR1, and CCR7 were found to be expressed by bone marrow-MSCs (BM-MSCs) in an in vitro study. CXCL12, CX3CL1, CXCL16, CCL19, and CCL3, all released by pancreatic cells, were combined using these receptors. The crosstalk mediated by these chemokines and receptors was thought to be a response to MSC migration into pancreas injury, and Sordi et al. proved this hypothesis. They confirmed that CXCR4-CXCL23 and CX3CR1-CX3CL1 mediated crosstalk between MSCs and pancreatic islets, and that systemically administering MSCs appeared to be the preferred method of MSCs homing to the injury site.

An eye glass on a book with many words maginifying the phrase "Diabetes type 1" with an insulin needle laying beside it
An eye glass on a book with many words maginifying the phrase "Diabetes type 1" with an insulin needle laying beside it

Generation Of Β Cells By Genetic Manipulation Of MSCs

Adenoviruses carrying three transcription factors (Ngn3, Pdx1, and MafA) have been shown to cause acinar cells to transform into β-cells in recent studies. That could be explained by this transition.

  • MafA promotes Pdx1 function, augments β-cell number, and pushes the maturation of newly generated β-cells.
  • Pdx1 aids deviation of β-cell fate.
  • Ngn3 stimulates acquisition of endocrine features.

Other studies have shown that overexpression of endocrine transcription factors can enforce interconversion between endocrine cells, such as to or to fate switches. During the embryonic stage, overexpression of Arx in Pax6+ endocrine precursors reduced and, but increased and PP β cells in the adult pancreas.

Key Factors Involving In IPCs Differentiation From HESCs

When human embryonic stem cells (hESCs) were cultured in suspension, Schuldiner et al. first demonstrated that they could spontaneously differentiate into insulin-producing cells (IPCs). Adherent hESCs could also express insulin in culture, according to Assady et al. This spontaneous differentiation pattern, however, had a low efficiency. Despite the fact that some researchers used gene manipulation to improve islet β-cell transduction efficiency by overexpressing Pdx1 or Ngn3, these methods were limited for future cell therapy due to contamination of exogenous DNA. In vitro, embryonic stem cells were programmed to differentiate into pancreatic β-cells in a step-by-step fashion.

Cells in conditional culture are being developed to mimic embryonic development. The first step inducing SCs toward definitive endoderm, the second step toward pancreatic or endocrine progenitors, and the third step toward cells are the three key developmental stages for generating islet β-cells.

Multiple Sources Of MSCs To Generate IPCs

It has been looked into using various factor combinations to induce hESCs into IPCs. The goal was to increase the quantity and maturity of IPCs, despite the fact that different MSC sources had different induction protocols.

In Vitro Differentiation Of Human BM-MSCs Into IPCs

IPCs can be made from adult BM-MSCs using conditional culturing. Mixed factors of EGF, bFGF, exending-4, and activin A could induce islet-cells to express insulin at both the mRNA and protein levels in high glucose DMEM (25 mmol/L) containing β-mercaptoethanol to promote stem cell differentiation. The differentiated IPCs were able to secrete C-peptide and normalize blood glucose levels in STZ-induced hyperglycemia mice for at least 9 weeks after being differentiated in a 4-step procedure.

In Vitro Differentiation Of Human Umbilical Cord MSCs Into IPCs

MSCs from the human umbilical cord can differentiate into IPCs in a differentiated medium. Wu et al. used a one-step method to create islet-like cell clusters that were able to express high levels of the pancreatic-specific transcription factor PDX-1 and the pancreatic-specific marker C-peptide. Apart from common factors such as activin-A, exendin-4, and HGF, the differentiation medium contained a hormone called pentagastrin. BM-MSCs formed smaller islet-like cell clusters and had lower levels of pdx1 and C-peptide in the same differentiation medium. Insulin-producing cells could be obtained without the formation of islet-like cell clusters using a three-step induction of Wharton's jelly MSCs. In STZ-induced mice, retro-orbital transplantation of differentiated IPCs may help to reduce hyperglycemia. Human umbilical cord MSCs were able to differentiate into IPCs in vitro and have a therapeutic effect in vivo.

Three syringe laying beside a stack of dice spelling out the phrase "diabetes type 1" in upper case
Three syringe laying beside a stack of dice spelling out the phrase "diabetes type 1" in upper case

In Vitro Differentiation Of Human Adipose Tissue-Derived MSCs Into IPCs

ADSCs derived from human adipose tissue have the ability to differentiate into insulin-producing cells. Jiyeon et al. used human adipose tissue-derived MSCs to achieve a pancreatic endocrine phenotype using a similar differentiation medium. To obtain similar embryoid bodies from ADSCs, Okura et al. used low-attachment culture dishes. They were able to obtain insulin-producing cells by following Segev et al.'s step-by-step methods for regenerating IPCs from embryoid bodies. Cells derived from ADSCs had functional similarities to pancreatic islet cells after 21 days of condition culture, such as clusters of insulin-and C-peptide-coexpressing cells and glucagon expression on the cell surface.

In Vitro Differentiation Of Human Endometrial Stromal Stem Cells (ESSC) Into IPCs

Mesenchymal stem cells can be isolated from human endometrium and differentiate into a variety of cell types, including chondrogenic, adipogenic, ostepgenic, neurogenic, and cardiogenic cells, according to research. As a result, the ability of ESSCs to differentiate into IPCs was examined. Using cDNA microarrays, it was possible to obtain insulin-secreting cells from ESSCs cultured in DMEM-LG supplemented with bFGF, EGF, and platelet-derived growth factor-BB. Xenotransplanting differentiated ESSCs into diabetic mice could help them regain control of their blood insulin levels.

People Also Ask

Could Stem Cells Be Used To Treat Type 1 Diabetes?

Stem cell therapy holds great potential for curing patients with T1DM. With the advent of research on stem cell therapy for various diseases, breakthroughs in stem cell-based therapy for T1DM have been reported.

Can Stem Cells Reverse Type 1 Diabetes?

Researchers believe that it is possible to replace the damaged islet cells with new healthy cells, but this might also require a way to prevent your body's immune system from attacking and destroying these new cells. This would essentially be a possible cure for type 1 diabetes. This is where stem cells come in.

What Type Of Stem Cells Treat Type 1 Diabetes?

Utilizing research from the Melton Lab, Vertex Pharmaceuticals has developed VX-880, an investigational stem cell-derived, fully differentiated pancreatic islet cell replacement therapy for people with type 1 diabetes (T1D).

What Is The Latest Treatment For Type 1 Diabetes?

Type 1 diabetes is an autoimmune disease that causes loss of pancreatic beta cells, which produce endogenous insulin. To replace that, patients must take exogenous insulin by shots or pump and are at risk of dangerous low blood sugar events. There is no current oral treatment for this disease.

Conclusion

Many advances have been made in the study of using MSCs to treat diabetes in animal models. By improving β cell loss and islet structure, direct MSC transplantation into hyperglycemic mice could lower blood glucose and extend lifespan. However, the hypoglycaemic effect was limited, and blood glucose levels remained higher than normal. To find the best therapeutic effect on diabetes models, researchers should look at hypoglycemic effect and mouse survival time over a longer period of time. MSC administration dose and frequency must also be investigated. Furthermore, the mechanism of MSC transplantation promoting β cell regeneration needs to be confirmed, and this finding could point the way to a more effective MSC-based diabetes treatment.

Share: Twitter | Facebook | Linkedin

About The Authors

Alexander McCaslin

Alexander McCaslin - My job is to promote your health and I will look out for your well-being and happiness.

Recent Articles

  • Sociopaths Vs Psychopaths - Shedding Light On Dark Personalities

    Sociology

    Sociopaths Vs Psychopaths - Shedding Light On Dark Personalities

    The word "versus/vs." in this phrase "Sociopaths vs. psychopaths" suggests that the two have contrasting differences. Sociopaths and psychopaths have often been depicted in popular media as cold-blooded killers or cunning manipulators. However, the reality of these disorders is much more complex.

  • Finding Spiritual Guidance Through Tarot And Divination - Unlocking Your Spiritual Path

    Tarot

    Finding Spiritual Guidance Through Tarot And Divination - Unlocking Your Spiritual Path

    Whether you're new to tarot and divination or have been practicing for a while, this article will discuss finding spiritual guidance through tarot and divination.

  • The Most Famous And Infamous Gamblers In History - Infamy And Fame In The World Of Gambling

    Celebs

    The Most Famous And Infamous Gamblers In History - Infamy And Fame In The World Of Gambling

    The world of gambling has seen its fair share of legendary figures, both good and bad. The most famous and infamous gamblers in history have left their mark on the industry, and their stories have become the stuff of legend.

  • Occult Spells - What Are These? And How To Use Them For Your Advantage

    Spells

    Occult Spells - What Are These? And How To Use Them For Your Advantage

    Playing around with occult spells is entertaining, particularly when most of them have hilariously disastrous results for your opponents. These are a means by which a Sorcerer, Witch, or Wizard may influence the course of events to produce an effect that serves their purposes.

  • The Psychology And Sociology Of Gambling Addiction - Understanding The Cause And Effect

    Sociology

    The Psychology And Sociology Of Gambling Addiction - Understanding The Cause And Effect

    The psychology and sociology of gambling addiction is a complex and multifaceted topic that has been the subject of extensive research and discussion in recent years. Gambling addiction, also known as compulsive gambling or problem gambling, is a behavioral disorder that can have serious consequences for individuals and their families.

  • Quinton Griggs - The Gen Z Heartthrob Taking Over The Internet

    Celebs

    Quinton Griggs - The Gen Z Heartthrob Taking Over The Internet

    Quinton Griggs is a young American social media personality who has gained massive popularity on the internet in recent years. He first rose to fame on the video-sharing app TikTok, where he garnered millions of followers with his entertaining videos and charming personality.

  • How To Win Money At The Casino Slot Machines - Improve Your Odds To Win

    Betting

    How To Win Money At The Casino Slot Machines - Improve Your Odds To Win

    How to win money at the casino slot machines focuses on tried-and-true ways to improve your odds instead of the general strategies you can find in any book about online casinos. It takes more than just trying to predict when a slot machine will pay out to learn how to choose a slot machine.

  • How To Improve Your Mental Health Through Gratitude Practice - Practical Tips And Strategies

    Health

    How To Improve Your Mental Health Through Gratitude Practice - Practical Tips And Strategies

    To know the answer to questions that how to improve your mental health through gratitude practice, you must know that mental health is an essential aspect of a person's overall well-being. It affects how a person thinks, feels, and acts, and it plays a significant role in their ability to cope with life's challenges.

  • Radio Waves - What They Tell Us About The Universe

    Astronomy

    Radio Waves - What They Tell Us About The Universe

    Stars shine brightly in the night sky, illuminating the darkness above us. Millions of them can be seen if you avoid bright lights and live in a remote area. The closest stars appear as discrete dots.

  • How Does A Round Robin Bet Work?

  • Adam DiMarco - A Versatile Actor On The Rise

  • How To Improve Your Mental Health Through Forest Bathing - Unlock The Benefits Of Forest Bathing

  • Meaning Of A Purple Butterfly - Symbols Of Transformation

  • Danielley Ayala - From Instagram Influencer To Entrepreneur