Nicotinamide induces both proliferation and differentiation of embryonic stem cells into insulin-producing cells

Vaca, Pilar; Berná, Genoveva; Martı́n, Franz; Soria, Bernat

doi:10.1016/s0041-1345(03)00735-8

Cited by 42 publications

(33 citation statements)

References 8 publications

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“…Another method of blocking in vitro differentiation of EPCs is the use of a vitamin B3 analogue-NAM, which inhibits several key enzymes that require NAD+, including the sirtuin family of histone/protein deacetylases (such as SIRT1) that regulate several biological pathways involving cell adhesion, migration, proliferation and differentiation (55)(56)(57)(58)(59). In preclinical studies, ex vivo treatment of CB CD34 + cells with NAM and cytokines led to their robust expansion (60,61).…”

Section: Nicotinamide (Nam)mentioning

confidence: 99%

Engineering cord blood to improve engraftment after cord blood transplant

Mehta¹,

Dave²,

Bollard³

et al. 2017

Stem Cell Investig.

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Umbilical cord blood transplant (CBT) has traditionally been associated with slower engraftment of neutrophils, delayed immune reconstitution and consequently higher risk of infections as compared with peripheral blood progenitor cell (PBPC) or bone marrow (BM) transplants. This is primarily due to low numbers of total nucleated cells (TNCs) and the naive nature of CB immune cells. The use of double unit CB transplant (DCBT) increases the total cell dose in the graft, but it still does not produce as rapid engraftment as seen with PBPC or even BM transplants. Herein, we discuss strategies to improve engraftment after CBT. We describe methods of (I) expansion of CB graft ex vivo to increase the total cell dose; and (II) enhancement of BM homing capability of CB progenitor cells; (III) ex vivo expansion of CB derived T cells for improving T cell function against viruses, tumors and protection from graft versus host disease (GVHD). With these novel approaches, engraftment after CBT is now reaching levels comparable to that of other graft types.

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Section: Nicotinamide (Nam)mentioning

confidence: 99%

Engineering cord blood to improve engraftment after cord blood transplant

Mehta¹,

Dave²,

Bollard³

et al. 2017

Stem Cell Investig.

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“…They noted that the insulin content of the cells increased 20-fold and that the cells showed a good insulin response to different secretagogues. Vaca et al 7 demonstrated that the combination of nutrient restriction and NA supplementation decreases the rate of proliferation and substantially increases the insulin content (1.780 ng insulin/mg protein) in D3 mouse embryonic stem cell culture, a value 3-fold greater than the values obtained by other authors, suggesting that NA may increase insulin synthesis. Therefore, NA plus nutrient restriction increases insulin content and improves the last steps in the maturation process under experimental conditions in which undesired proliferation is controlled.…”

Section: Discussionmentioning

confidence: 91%

“…7 Moreover, several protocols have used NA as a differentiation factor. 26 NA is also suggested to have a stimulatory effect on islet regeneration.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, increases in insulin production and content of cultured fetal pig islet-like cell clusters have been seen as a consequence of beta-cell neoformation through differentiation. 7 Hence, in stem cell research, several protocols have used NA as a differentiation factor. 8 Preliminary data from the literature support the involvement of macrophage migration inhibitory factor (MIF) in stimulating insulin secretion.…”

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confidence: 99%

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Nicotinamide-functionalized multiwalled carbon nanotubes increase insulin production in pancreatic beta cells via MIF pathway

Ilie¹,

Ilie²,

Mocan³

et al. 2013

IJN

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“…Additional work has indicated that nicotinamide can increase cell tolerance against vascular thermal injury and increase capillary density [130]. Yet what may be more significant is the capacity of nicotinamide to foster cellular proliferation and Development, Nicotinamide can promote the maturation of fetal cells [131], the proliferation and differentiation of embryonic stem cells to yield insulin-producing cells [132], assist with trophic regulation to generate insulin secreting cells from adult pancreatic exocrine cells [133], and enhance an adaptive response to physical and chemical agents in mouse bone marrow cells that consists of an error-free DNA repair mechanism [134]. Nicotinamide also appears to be a critical requirement to promote the effective biological function of some embryonic stem cells.…”

Section: Nicotinamide Progenitor Cells and Cellular Proliferationmentioning

confidence: 99%

Cell Life Versus Cell Longevity: The Mysteries Surrounding the NAD+ Precursor Nicotinamide

Chong²,

Maiese³

2006

CMC

114

167

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Nicotinamide, the amide form of niacin (vitamin B 3 ), is the precursor for the coenzyme β-nicotinamide adenine dinucleotide (NAD + ) and plays a significant role during the enhancement of cell survival as well as cell longevity. Yet, these abilities of nicotinamide appear to be diametrically opposed. Here we describe the development of nicotinamide as a novel agent that is critical for modulating cellular metabolism, plasticity, longevity, and inflammatory microglial function as well as for influencing cellular life span. The capacity of nicotinamide to govern not only intrinsic cellular integrity, but also extrinsic cellular inflammation rests with the modulation of a host of cellular targets that involve mitochondrial membrane potential, poly(ADP-ribose) polymerase, protein kinase B (Akt), Forkhead transcription factors, Bad, caspases, and microglial activation. Further knowledge acquired in regards to the ability of nicotinamide to foster cellular survival and regulate cellular lifespan should significantly promote the development of therapies against a host of disorders, such as aging, Alzheimer's disease, diabetes, cerebral ischemia, Parkinson's disease, and cancer. KeywordsAkt; Alzheimer's disease; apoptosis; caspases; diabetes; erythropoietin; Huntington's disease; microglia; NAD + ; Parkinson's disease; stroke; vitamin B 3 NICOTINAMIDE, NAD + PRECURSOR, AND CELLULAR METABOLISMAs the amide form of niacin or vitamin B 3 , nicotinamide is the precursor for the coenzyme β-nicotinamide adenine dinucleotide (NAD + ) and is essential for the synthesis of nicotinamide adenine dinucleotide phosphate (NADP + ) [1,2]. Nicotinamide and nicotinic acid can be obtained either through synthesis in the body or through a dietary source [3]. The predominant form of niacin in dietary plant sources is nicotinic acid that is rapidly absorbed through the gastrointestinal epithelium. Nicotinamide is formed through the conversion of nicotinic acid in the liver or through the hydrolysis of NAD + . Once nicotinamide is obtained in the body, it is utilized to synthesize NAD + [4].Nicotinamide through NAD + plays a critical physiological role in cellular metabolism and can be directly utilized by cells to synthesize NAD + [4]. Nicotinamide also participates in energy metabolism through the tricarboxylic acid cycle by utilizing NAD + in the mitochondrial respiratory electron transport chain for the production of ATP, DNA synthesis, and DNA repair *Address correspondence to this author at the Department of Neurology, 8C-1 UHC, Wayne State University School of Medicine, 4201 St. Antoine, Detroit, MI 48201, USA; Fax: 313-966-0486; E-mail: kmaiese@med.wayne.edu. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript [5][6][7]. Furthermore, nicotinamide can significantly increase NAD + levels in vulnerable regions of the ischemic brain, suggesting that nicotinamide may offer cytoprotection of injured tissue through the maintenance of NAD + levels [8]. Administration of nicotinamide can signif...

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Nicotinamide induces both proliferation and differentiation of embryonic stem cells into insulin-producing cells

Cited by 42 publications

References 8 publications

Engineering cord blood to improve engraftment after cord blood transplant

Engineering cord blood to improve engraftment after cord blood transplant

Nicotinamide-functionalized multiwalled carbon nanotubes increase insulin production in pancreatic beta cells via MIF pathway

Cell Life Versus Cell Longevity: The Mysteries Surrounding the NAD+ Precursor Nicotinamide

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