Transplantation of stem cells from umbilical cord blood as therapy for type I diabetes

Stiner, Rachel; Alexander, Michael P.; Liu, Guangyang; Liao, Wenbin; Liu, Yongjun; Yu, Jiwei; Pone, Egest J.; Zhao, Weian; Lakey, Jonathan R. T.

doi:10.1007/s00441-019-03046-2

Cited by 30 publications

(23 citation statements)

References 78 publications

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“…Mesenchymal stem cells (MSCs), kind of bone marrow-derived cells, are capable of differentiating into multiple cell types because of their self-renewing ability and multipotent progenitors 10. At present, MSCs have been most widely used in biological tissue repair and engineering, such as in respiratory system disease,11 nervous system disease,12 endocrine system disease,13,14 cardiovascular system disease,15 etc. Therefore, utilizes MSCs from the bone marrow to migrate toward the injury site and stimulate into chondrocytes to repair bone defect, is a promising choice for comminuted fracture repair 16,17.…”

Section: Introductionmentioning

confidence: 99%

<p>Novel Aptamer-Functionalized Nanoparticles Enhances Bone Defect Repair By Improving Stem Cell Recruitment</p>

Wang¹,

Wu²,

Qiao³

et al. 2019

IJN

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BackgroundThe restoration and repair method in the clinic of delayed fracture healing and non-union after comminuted fractures are urgently needed to improve the prognosis of patients. The recruitment of endogenous stem cells has been considered a promising approach in bone defect repair.ProposeThe aim of this study was to generate a de novel MSCs aptamer and developed the first, feasible, economical, bio-compatible, and functional MSCs aptamer-directed nanoparticles without complex manufacture to recruit mesenchymal stem cells (MSCs) for bone defect regeneration.MethodsWhole-cell SELEX was used to generate a de novel MSCs aptamer. Flow cytometry was applied to assess the binding specificities, affinities and sorting abilities of the aptamers. Nano-Aptamer Ball (NAB) was constructed by NHS/EDC reaction. The diameter and zeta of NAB were assessed by dynamic light scattering. CCK8 assay was utilized to evaluate whether NAB could cause non-specific cytotoxicity and induce cell proliferation. To evaluate the bone repair capacity of NAB, histomorphological staining, alizarin red and micro X-ray were used to observe the repair degree of defect in vivo. ELISA was used to detect osteopontin (OPN), osteocalcin (BGP) by, and alkaline phosphatase (ALP) in peripheral blood.ResultsMSCs aptamer termed as HM69 could bind with MSCs with high specificity and Kd of 9.67 nM, while has minimal cross-reactivities to other negative cells. HM69 could capture MSCs with a purity of >89%. In vitro, NAB could bind and capture MSCs effectively, whereas did not cause obvious cytotoxicity. In vivo, serum OPN, BGP, and ALP levels in the NAB group of rats were increased at both 2 and 4 weeks, indicating the repair and osteogenesis generation. The healing of bone defects in the NAB group was significantly better than control groups, the defects became blurred, and local trabecular bone growth could be observed in X-ray. The organized hematoma and cell growth in the bone marrow of the NAB group were more vigorous in bone sections staining.ConclusionThese suggested that HM69 and HM69-functionalized nanoparticles NAB exhibited the ability to recruit MSCs both in vitro and in vivo and achieved a better outcome of bone defect repair in a rat model. The findings demonstrate a promising strategy of using aptamer-functionalized bio-nanoparticles for the restoration of bone defects via aptamer-introduced homing of MSCs.

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Section: Introductionmentioning

confidence: 99%

<p>Novel Aptamer-Functionalized Nanoparticles Enhances Bone Defect Repair By Improving Stem Cell Recruitment</p>

Wang¹,

Wu²,

Qiao³

et al. 2019

IJN

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“…The overall results of the carried out meta-analyses provide a moderate quality evidence suggesting the better therapeutic outcome of WJ-MSCs over UCB in both T1DM and T2DM. During the past few years, the therapeutic potential of both WJ-MSCs and UCB for DM has ignited great interest [46,47]. In addition, several meta-analysis studies recently reported the clinical efficacy of various types of stem cells for treating DM with several degrees of therapeutic efficacy [9,48].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic efficacy of umbilical cord-derived stem cells for diabetes mellitus: a meta-analysis study

Kassem

Kamal

2020

Stem Cell Res Ther

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Background Stem cell therapy provides great hope for patients with diabetes mellitus (DM). DM is a seriously alarming metabolic disease characterized by hyperglycemia and β cell dysfunction. Efficient novel therapeutic modalities to treat DM are indeed warranted. Stem cells (SC) derived from the umbilical cord specifically provide several advantages and unique characteristics being a readily available non-invasive source, with an additional credit for their banking potential. This meta-analysis study aims to provide a focused assessment for therapeutic efficacy of umbilical cord (UC)-derived SC-transplantation, namely Wharton’s jelly mesenchymal stem cells (WJ-MSCs) and umbilical cord blood (UCB) for DM. Methods The clinical efficacy was evaluated based on glycemic control status (reflected on HbA1c%) and β cell function (reflected on C-peptide levels), as well as the daily insulin requirement in diabetic patients after receiving UC-derived SC-transplantation compared to baseline values. Moreover, we assessed these outcome measures in patients who received such intervention compared to those who did not receive it in randomized/non-randomized controlled clinical trials. We employed a random-effects model and standardized mean difference for this meta-analysis. Results Eleven eligible clinical studies were included; WJ-MSCs (6 studies; 172 patients including 71 controls) and UCB (5 studies; 74 patients including 15 controls). WJ-MSCs significantly improved HbA1c% (pooled-estimate − 1.085; 95%CI (− 1.513, − 0.657); p < 0.001) and C-peptide levels (pooled-estimate 1.008; 95%CI (0.475, 1.541); p < 0.001), as well as the daily insulin-requirement (pooled-estimate − 2.027; 95%CI (− 3.32, − 0.733); p = 0.002). On the contrary, UCB was found to be uniformly ineffective; HbA1c% (pooled-estimate − 0.091, 95%CI (− 0.454, 0.271); p = 0.622), significantly deteriorated C-peptide levels (pooled-estimate − 0.789; 95%CI (− 1.252, − 0.325); p < 0.001) and daily insulin-requirement (pooled-estimate 0.916; 95%CI (0.247, 1.585); p = 0.007). All these observations remained consistent when we carried out sub-group meta-analysis for T1DM and T2DM and also when we compared patients who received WJ-MSCs or UCB to controls. Conclusions The results of our meta-analysis provide a clear evidence for the superior efficacy of WJ-MSCs over UCB in DM. This sheds lights on the importance to consider banking of WJ-MSCs together with the well-established routine UCB-banking, especially for those with family history of DM. Additionally, further clinical studies are required to investigate therapeutic efficacy of selected/enriched UCB-derived cell populations with immunomodulatory/regenerative potential in DM.

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“…Very promising results have been achieved with both the administration models and, on the other hand, both ways present potential pitfalls and limits. In this review, we will discuss the most promising results obtained with MSCs for the treatment of diabetes and its complications; we will compare the different therapeutic treatments applied as well as the most likely mechanisms of action and overall we will give an in-depth overview of the pros and the cons of the use of MSCs for the therapy of both T1D and T2D [17,19,20].…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

“…Concerning the effect on islet survival, the analysis of MSCs secretoma revealed that these cells release a plethora of soluble factors with a trophic action on pancreatic beta cells, as well as a number of anti-inflammatory cytokines, antioxidant factors and anti-apoptotic molecules, which could theoretically relieve the inflammatory milieu favorable to diabetes onset and to insulin resistance development [22]. Besides such paracrine effects on pancreatic islets, MSCs could also exert a positive action through direct contact with pancreatic islets: after this mutual interaction, they can start to release insulin, thus becoming insulin producing cells [18,20]. Many mechanisms may be involved in such a direct stimulation between MSCs and pancreatic islets, most of them are still unknown, although it has been proposed an important role of the extracellular matrix proteins [23], as well as of the exosomes (and more generally extracellular vesicles) exchange.…”

Section: In Vitro Studiesmentioning

confidence: 99%

Mesenchymal Stem Cells: A Trump Card for the Treatment of Diabetes?

Donzelli

Scuteri

2020

Biomedicines

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The advent of the new revolutionary approach based on regenerative medicine is progressively reshaping the therapeutic scenario of many different diseases, such as cardiovascular diseases and immune diseases, with encouraging results. During the last 10 years, many studies have also proposed the use of mesenchymal stem cells (MSCs), adult stem cells with several interesting properties already used in different experimental models, for the treatment of diabetes, however, reporting conflicting outcomes. These reasons have given rise to a question: are these cells a real trump card for the biomedical field? Are they really able to outclass the traditional therapies, or at least able to give an advantage over them? In this review, we will discuss the most promising results obtained with MSCs for the treatment of diabetes and its complications, we will compare the different therapeutic treatments applied as well as the most likely mechanisms of action, and overall we will give an in-depth overview of the pros and the cons of the use of MSCs for the therapy of both type-1 and type-2 diabetes.

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Transplantation of stem cells from umbilical cord blood as therapy for type I diabetes

Cited by 30 publications

References 78 publications

<p>Novel Aptamer-Functionalized Nanoparticles Enhances Bone Defect Repair By Improving Stem Cell Recruitment</p>

<p>Novel Aptamer-Functionalized Nanoparticles Enhances Bone Defect Repair By Improving Stem Cell Recruitment</p>

Therapeutic efficacy of umbilical cord-derived stem cells for diabetes mellitus: a meta-analysis study

Mesenchymal Stem Cells: A Trump Card for the Treatment of Diabetes?

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