Insulin - producing cells derived from stem cells: recent progress and future directions

The use of stem cells in cell therapies has shown promising results in the treatment of several diseases, including diabetes mellitus, in both humans and animals. Mesenchymal stem cells (MSCs) can be isolated from various locations, including bone marrow, adipose tissues, synovia, muscles, dental pulp, umbilical cords, and the placenta. In vitro, by manipulating the composition of the culture medium or transfection, MSCs can differentiate into several cell lineages, including insulin-producing cells (IPCs). Unlike osteogenic, chondrogenic, and adipogenic differentiation, for which the culture medium and time are similar between studies, studies involving the induction of MSC differentiation in IPCs differ greatly. This divergence is usually evident in relation to the differentiation technique used, the composition of the culture medium, the cultivation time, which can vary from a few hours to several months, and the number of steps to complete differentiation. However, although there is no “gold standard” differentiation medium composition, most prominent studies mention the use of nicotinamide, exedin-4, ß-mercaptoethanol, fibroblast growth factor b (FGFb), and glucose in the culture medium to promote the differentiation of MSCs into IPCs. Therefore, the purpose of this review is to investigate the stages of MSC differentiation into IPCs both in vivo and in vitro, as well as address differentiation techniques and molecular actions and mechanisms by which some substances, such as nicotinamide, exedin-4, ßmercaptoethanol, FGFb, and glucose, participate in the differentiation process.

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A Review of Evaluating Hematopoietic Stem Cells Derived from Umbilical Cord Blood's Expansion and Homing

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200124115444 ◽

2020 ◽

Vol 15 (3) ◽

pp. 250-262

Author(s):

Maryam Islami ◽

Fatemeh Soleimanifar

Keyword(s):

Stem Cells ◽

Hematopoietic Stem Cells ◽

Umbilical Cord ◽

Stromal Cells ◽

Ex Vivo ◽

Hematologic Malignancies ◽

Future Directions ◽

Hematopoietic Stem ◽

Efficient Procedure ◽

Hematopoietic Recovery

Transplantation of hematopoietic stem cells (HSCs) derived from umbilical cord blood (UCB) has been taken into account as a therapeutic approach in patients with hematologic malignancies. Unfortunately, there are limitations concerning HSC transplantation (HSCT), including (a) low contents of UCB-HSCs in a single unit of UCB and (b) defects in UCB-HSC homing to their niche. Therefore, delays are observed in hematopoietic and immunologic recovery and homing. Among numerous strategies proposed, ex vivo expansion of UCB-HSCs to enhance UCB-HSC dose without any differentiation into mature cells is known as an efficient procedure that is able to alter clinical treatments through adjusting transplantation-related results and making them available. Accordingly, culture type, cytokine combinations, O2 level, co-culture with mesenchymal stromal cells (MSCs), as well as gene manipulation of UCB-HSCs can have effects on their expansion and growth. Besides, defects in homing can be resolved by exposing UCB-HSCs to compounds aimed at improving homing. Fucosylation of HSCs before expansion, CXCR4-SDF-1 axis partnership and homing gene involvement are among strategies that all depend on efficiency, reasonable costs, and confirmation of clinical trials. In general, the present study reviewed factors improving the expansion and homing of UCB-HSCs aimed at advancing hematopoietic recovery and expansion in clinical applications and future directions.

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Dual‐hormone artificial pancreas for management of type 1 diabetes: Recent progress and future directions

Artificial Organs ◽

10.1111/aor.14023 ◽

2021 ◽

Author(s):

Marco Infante ◽

David A. Baidal ◽

Michael R. Rickels ◽

Andrea Fabbri ◽

Jay S. Skyler ◽

...

Keyword(s):

Type 1 Diabetes ◽

Recent Progress ◽

Artificial Pancreas ◽

Future Directions

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Tailored generation of insulin producing cells from canine mesenchymal stem cells derived from bone marrow and adipose tissue

Scientific Reports ◽

10.1038/s41598-021-91774-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Watchareewan Rodprasert ◽

Sirirat Nantavisai ◽

Koranis Pathanachai ◽

Prasit Pavasant ◽

Thanaphum Osathanon ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Hanging Drop ◽

Differentiation Potential ◽

Insulin Producing Cells ◽

Edmonton Protocol ◽

Effective Generation ◽

Hanging Drop Culture ◽

Peptide Secretion

AbstractThe trend of regenerative therapy for diabetes in human and veterinary practices has conceptually been proven according to the Edmonton protocol and animal models. Establishing an alternative insulin-producing cell (IPC) resource for further clinical application is a challenging task. This study investigated IPC generation from two practical canine mesenchymal stem cells (cMSCs), canine bone marrow-derived MSCs (cBM-MSCs) and canine adipose-derived MSCs (cAD-MSCs). The results illustrated that cBM-MSCs and cAD-MSCs contain distinct pancreatic differentiation potential and require the tailor-made induction protocols. The effective generation of cBM-MSC-derived IPCs needs the integration of genetic and microenvironment manipulation using a hanging-drop culture of PDX1-transfected cBM-MSCs under a three-step pancreatic induction protocol. However, this protocol is resource- and time-consuming. Another study on cAD-MSC-derived IPC generation found that IPC colonies could be obtained by a low attachment culture under the three-step induction protocol. Further, Notch signaling inhibition during pancreatic endoderm/progenitor induction yielded IPC colonies through the trend of glucose-responsive C-peptide secretion. Thus, this study showed that IPCs could be obtained from cBM-MSCs and cAD-MSCs through different induction techniques. Also, further signaling manipulation studies should be conducted to maximize the protocol’s efficiency.

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Will mesenchymal stem cells be future directions for treating radiation-induced skin injury?

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02261-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Zhuoqun Fang ◽

Penghong Chen ◽

Shijie Tang ◽

Aizhen Chen ◽

Chaoyu Zhang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Malignant Tumors ◽

Skin Injury ◽

Future Directions ◽

Cytokines And Chemokines ◽

Radiation Induced ◽

The Common ◽

Apoptotic Activity ◽

Different Sources

AbstractRadiation-induced skin injury (RISI) is one of the common serious side effects of radiotherapy (RT) for patients with malignant tumors. Mesenchymal stem cells (MSCs) are applied to RISI repair in some clinical cases series except some traditional options. Though direct replacement of damaged cells may be achieved through differentiation capacity of MSCs, more recent data indicate that various cytokines and chemokines secreted by MSCs are involved in synergetic therapy of RISI by anti-inflammatory, immunomodulation, antioxidant, revascularization, and anti-apoptotic activity. In this paper, we not only discussed different sources of MSCs on the treatment of RISI both in preclinical studies and clinical trials, but also summarized the applications and mechanisms of MSCs in other related regenerative fields.

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