Witold Norbert Nowak

Witold Norbert Nowak
Jagiellonian University | UJ · Department of Medical Biotechnology

PhD

About

61
Publications
8,454
Reads
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1,048
Citations
Additional affiliations
January 2018 - present
Jagiellonian University
Position
  • Research Associate
September 2015 - December 2017
King's College London
Position
  • Research Associate
January 2012 - September 2015
Jagiellonian University
Position
  • Research Assistant

Publications

Publications (61)
Article
Full-text available
Aims/Introduction Type 2 diabetes is often complicated by diabetic foot syndrome (DFS). We analyzed the circulating stem cells, growth factor and anti‐oxidant gene expression profiles in type 2 diabetes patients without or with different forms of DFS. Materials and Methods Healthy volunteers (n = 13) and type 2 diabetes patients: (i) without DFS (...
Article
Atherosclerosis is the key component of most cardiovascular diseases, including stroke and myocardial infarction.1–3 An inflamed endothelium recruits inflammatory cells, such as monocytes, via the expression of various mediators and chemokines.4–6 This, in addition to the accumulation of cholesterol and smooth muscle cells (SMCs) in the intima, lea...
Article
Full-text available
Aims: Mesenchymal stromal cells (MSCs) are heterogeneous cells from adult tissues, able to differentiate in vitro into adipocytes, osteoblasts or chondrocytes. Such cells are widely studied in regenerative medicine. However, the success of cellular therapy depends on the cell survival. Heme oxygenase-1 (HO-1, encoded by the Hmox1 gene), an enzyme c...
Article
Full-text available
Rationale: Transplantation-accelerated arteriosclerosis is one of the major challenges for long-term survival of patients with solid organ transplantation. Although stem/progenitor cells (SPCs) have been implicated to participate in this process, the cells of origin and underlying mechanisms have not been fully defined. Objective: The objective of...
Article
Objective: Perivascular adipose tissue (PVAT) plays a vital role in maintaining vascular homeostasis. However, most studies ascribed the function of PVAT in vascular remodeling to adipokines secreted by the perivascular adipocytes. Whether mesenchymal stem cells exist in PVAT and play a role in vascular regeneration remain unknown. Approach and Re...
Article
Full-text available
Melanoma-initiating cells (MICs) contribute to the tumorigenicity and heterogeneity of melanoma. MICs are identified by surface and functional markers and have been shown to display cancer stem cell (CSC) properties. However, the existence of MICs that follow the hierarchical CSC model has been questioned by studies showing that single unselected m...
Article
Myszy są podstawowym modelem badawczym w biologii i fizjologii. Jednak, aby móc badać na modelach mysich ludzką fizjologię oraz rozwój chorób specyficznych dla ludzi, należało stworzyć nowe ich szczepy. W tym celu opracowano myszy humanizowane, które wykazują ekspresję ludzkich genów albo mają przeszczepione ludzkie tkanki lub komórki. W niniejszej...
Article
Full-text available
Whilst the survival rates of childhood acute lymphoblastic leukemia (ALL) have increased remarkably over the last decades, the therapy resistance and toxicity are still the major causes of treatment failure. It was shown that overexpression of heme oxygenase-1 (HO-1) promotes proliferation and chemoresistance of cancer cells. In humans, the HO-1 ge...
Article
Full-text available
G-quadruplexes (G4) are stacked nucleic acid structures that are stabilized by heme. In cells, they affect DNA replication and gene transcription. They are unwound by several helicases but the composition of the repair complex and its heme sensitivity are unclear. We found that the accumulation of G-quadruplexes is affected by heme oxygenase-1 (Hmo...
Article
Full-text available
Stem/progenitor cells (SPCs) have been implicated to participate in vascular repair. However, the exact role of SPCs in endothelial repair of large vessels still remains controversial. This study aimed to delineate the cellular heterogeneity and possible functional role of endogenous vascular SPCs in large vessels. Using single-cell RNA-sequencing...
Article
Full-text available
While intrinsic changes in aging hematopoietic stem cells (HSCs) are well characterized, it remains unclear how extrinsic factors affect HSC aging. Here, we demonstrate that cells in the niche-endothelial cells (ECs) and CXCL12-abundant reticular cells (CARs)-highly express the heme-degrading enzyme, heme oxygenase 1 (HO-1), but then decrease its e...
Article
Full-text available
Granulocyte colony‐stimulating factor (G‐CSF) is used in clinical practice to mobilize cells from the bone marrow to the blood; however, it is not always effective. We show that cobalt protoporphyrin IX (CoPP) increases plasma concentrations of G‐CSF, IL‐6, and MCP‐1 in mice, triggering the mobilization of granulocytes and hematopoietic stem and pr...
Article
Full-text available
Moderate intravascular hemolysis is a common condition in newborns. It is followed by the accumulation of bilirubin, which is a secondary product of the activity of heme oxygenase-1, an enzyme that catalyzes the breakdown of heme released from disrupted erythrocytes and taken up by hepatic macrophages. Although these cells are a major site of enzym...
Article
Full-text available
Myeloid angiogenic cells (MAC) derive from hematopoietic stem/progenitor cells (HSPCs) that are mobilized from the bone marrow. They home to sites of neovascularization and contribute to angiogenesis by production of paracrine factors. The number and function of proangiogenic cells are impaired in patients with diabetes or cardiovascular diseases....
Article
Full-text available
NF-κB signaling, acting through NFKB1 dependent canonical and NFKB2 dependent non-canonical pathways plays a critical role in inflammatory and immune responses. Recent studies have associated mutations in these two genes with a common variable immunodeficiency (CVID). While evaluating a female patient seeking a diagnosis explaining her recurrent in...
Preprint
Full-text available
While intrinsic changes in aging hematopoietic stem cells (HSCs) are well-characterized, it remains unclear how hematopoietic niche affects HSC aging. Here, we demonstrate that cells in the niche - endothelial cells (ECs) and CXCL12-abundant reticular cells (CARs) - highly express the heme-degrading enzyme, heme oxygenase 1 (HO-1), but then decreas...
Article
Aging is the most critical risk factor for the development of cardiovascular diseases and their complications. Therefore, the fine-tuning of cellular response to getting older is an essential target for prospective therapies in cardiovascular medicine. One of the most promising targets might be the transcription factor Nrf2, which drives the expres...
Article
Full-text available
Heme oxygenase-1 (HO-1; encoded by Hmox1), a downstream target of the Nrf2 transcription factor, has been postulated to be a negative regulator of osteoclasts (OCLs) differentiation. Here, we further explored such a hypothesis by examining HO-1 effects in different stages of osteoclastogenesis. We confirmed the inhibition of the expression of OCLs...
Article
Full-text available
Tissue-engineered vascular grafts with long-term patency are greatly needed in the clinical settings, and smooth muscle cells (SMCs) are a critical graft component. Human mesenchymal stem cells (MSCs) are used for generating SMCs and understanding the underlying regulatory mechanisms of the MSC-to-SMC differentiation process could improve SMC gener...
Article
Full-text available
Tissue-engineered vascular grafts with long-term patency are greatly needed in the clinical settings, and smooth muscle cells (SMCs) are a critical graft component. Human mesenchymal stem cells (MSCs) are used for generating SMCs, and understanding the underlying regulatory mechanisms of the MSC-to-SMC differentiation process could improve SMC gene...
Article
Full-text available
Objective: Leptin is an adipokine initially thought to be a metabolic factor. Recent publications have shown its roles in inflammation and vascular disease, to which Sca-1(+) vascular progenitor cells within the vessel wall may contribute. We sought to elucidate the effects of leptin on Sca-1(+) progenitor cells migration and neointimal formation...
Article
Significance: The belief in the potency of stem cells has resulted in the medical applications of numerous cell types for organ repair, often with the low adherence to methodological stringency. Such uncritical enthusiasm is mainly presented in the approaches employing so-called mesenchymal stem cells (MSC), for the treatment of numerous, unrelate...
Article
Full-text available
Adventitial progenitor cells, including SCA-1⁺ and mesenchymal stem cells, are believed to be important in vascular remodeling. It has been shown that SCA-1⁺ progenitor cells are involved in neointimal hyperplasia of vein grafts, but little is known concerning their involvement in hyperlipidemia-induced atherosclerosis. We employed single-cell sequ...
Article
Conservative therapy after complete revascularization is increasing in popularity in patients with peripheral artery disease (PAD). The aim of the current study was to find determinants of the improvement of walking abilities and endothelial function in patients with PAD undergoing supervised treadmill training program (STTP). The presented study e...
Article
Heme oxygenase-1 (HO-1) is stress-inducible, cytoprotective enzyme degrading heme to carbon monoxide (CO), biliverdin and Fe²⁺. We showed that HO-1 knock-out mice (HO-1−/−) have a twofold higher level of granulocytes than wild type (WT) mice, despite decreased concentration of granulocyte colony-stimulating factor (G-CSF) in the blood and reduced s...
Article
Heme oxygenase-1 (HO-1) is stress-inducible, cytoprotective enzyme degrading heme to carbon monoxide (CO), biliverdin and Fe²⁺. We showed that HO-1 knock-out mice (HO-1−/−) have a twofold higher level of granulocytes than wild type (WT) mice, despite decreased concentration of granulocyte colony-stimulating factor (G-CSF) in the blood and reduced s...
Article
Induced pluripotent stem cells (iPSCs) have shown great potential in regenerative medicine and research applications like disease modeling or drug discovery. Endothelium is indispensable for vascular homeostasis, whereas endothelial dysfunction could lead to different diseases. Therefore, generating autologous cells, able to restore the endothelial...
Article
Clozapine is an effective atypical antipsychotic drug that unfortunately exhibits poor oral bioavailability. Moreover, the clinical use of the compound is limited because of its numerous unfavorable and unsafe side effects. Therefore, the aim of the present study was the development of a new nanocarrier for a more effective clozapine delivery. Here...
Article
Full-text available
Hypoxia-inducing pathologies as cancer develop pathologic and inefficient angiogenesis which rules tumor facilitating microenvironment, a key target for therapy. As such, the putative ability of endothelial precursor cells (EPCs) to specifically home to hypoxic sites of neovascularization prompted to design optimized, site-specific, cell-mediated,...
Article
Full-text available
Stem cells are self-renewing cells that can differentiate into specialized cell type(s). Pluripotent stem cells, i.e. embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) differentiate into cells of all three embryonic lineages. Multipotent stem cells, like hematopoietic stem cells (HSC), can develop into multiple specialized cells i...
Article
Full-text available
The pathogenesis of the abdominal aortic aneurysm (AAA) shows several hallmarks of atherosclerotic and atherothrombotic disease, but comprises an additional, predominant feature of proteolysis resulting in the degradation and destabilization of the aortic wall. This review aims to summarize the current knowledge on AAA development, involving the ac...
Article
Full-text available
C57BL/6 is the most often used laboratory mouse strain. However, sometimes it is beneficial to cross the transgenic mice on the C57BL/6 background to the other strain, such as FVB. Although this is a common strategy, the influence of crossing these different strains on homeostatic expression of cytokines is not known. Here we have investigated the...
Poster
Full-text available
miR378 is a microRNA commonly found in high levels is muscle tissue and is known to play roles in metabolism, muscle differentiation and it was found to play an antagonistic role together with hemeoxigenase in tumor angiogenesis. To test our hypothesis of the involvement of miR378 in blood vessel formation and regeneration processes in muscles we u...
Article
In their recent paper published in Stem Cells and Development Suszynska et al. (Stem Cells Dev 2013 Dec 3. [Epub ahead of print]) discussed the strategies of analysing the so called very small embryonic-like cells (VSELs), defined as Lin<sup>-</sup>Sca-1<sup>+</sup>CD45<sup>-</sup>FSC<sup>low</sup>, which were claimed to be the pluripotent stem cel...
Article
Purpose: Retinal degenerative diseases targeting the RPE and adjacent photoreceptors affect millions of people worldwide. The field of stem cell- and gene-based therapy holds great potential for the treatment of such diseases. The present study sought to graft genetically engineered mesenchymal stem cells (MSCs) that continuously produce neurotrop...
Article
Full-text available
Murine very small embryonic-like (VSEL) cells, defined by the Lin(-)Sca-1(+)CD45(-) phenotype and small size, were described as pluripotent cells and proposed to be the most primitive hematopoietic precursors in adult bone marrow. Although their isolation and potential application rely entirely on flow cytometry, the immunophenotype of VSELs has no...
Data
Analysis of melt curves of products amplified with primers used in earlier studies (Oct-4) [6], [9], [24] and with primers used in the current study (Oct-4A) [21] in sorted Lin−Sca-1+CD45−FSClow, bone marrow, and ESD3 (positive control) cDNAs, or in no RT and gDNA samples (negative controls). Primers used in earlier studies generated similar melt c...
Data
Sorting protocol for the single cell-derived colony assay. (A) Sorting strategy of collecting Lin−Sca-1+CD45−c-Kit+FSClow and Lin−Sca-1+CD45+c-Kit+ cells. (B) Sorting strategy of collecting SKL CD45−CD105+ and SKL CD45+CD105dim cells. (TIF)
Data
Gating strategy for ImageStream analysis. (TIF)
Data
(A) Representative analysis of size distribution in Lin−Sca-1+CD45−c-Kit− cell population. (B) Representative pictures showing morphology of Lin−Sca-1+CD45−c-Kit+ cells. ImageStream System. (TIF)
Data
Flow cytometry analysis showing that SKL CD45−CD105+ subset significantly overlaps with Lin−Sca-1+CD45−c-Kit+FSClow subpopulation, with more than 70% of Lin−Sca-1+CD45−c-Kit+FSClow being CD105-positive. (TIF)
Article
Vascular endothelium is the layer of cells that line blood vessels and serve as the primary barrier between the blood and the tissues. These cells play many important functions such as regulation of the vascular tone, blood flow and pressure control, maintaining the balance between thrombosis and fibrinolysis, participation in immune system reactio...
Article
Endothelium has an immense impact on the tissue regeneration, regulation of atherosclerosis and tumour growth. Therefore, modification of endothelial cell differentiation and function seems a promising target for many therapies. MicroRNAs are small RNA molecules, which recognize and inhibit specific mRNAs. In that way, they can regulate and orchest...
Article
Full-text available
Exercise training remains a therapy of choice in intermittent claudication (IC). However, too exhaustive exercise may cause ischaemic injury and inflammatory response. We tested the impact of three-month treadmill training and single treadmill exercise on antioxidant gene expressions, cytokine concentrations and number of marrow-derived proangiogen...
Article
Full-text available
Recently we have shown that hypoxia as well as overexpression of the stable form of hypoxia-inducible factor-1α (HIF-1α) diminished the expression of interleukin-8 (IL-8) by inhibition of the Nrf2 transcription factor in HMEC-1 cells. Because HIF isoforms may exert different effects, we aimed to examine the influence of HIF-2α on IL-8 expression in...
Article
Full-text available
Heme oxygenase-1 (HO-1) is an antioxidative and cytoprotective enzyme, which may protect neoplastic cells against anticancer therapies, thereby promoting the progression of growing tumors. Our aim was to investigate the role of HO-1 in cancer induction. Experiments were performed in HO-1(+/+), HO-1(+/-), and HO-1(-/-) mice subjected to chemical ind...
Article
Heme oxygenase-1 (HMOX1) is a cytoprotective enzyme degrading heme to biliverdin, iron ions, and carbon monoxide, whose expression is induced in response to oxidative stress. Its overexpression has been suggested as a strategy improving survival of transplanted muscle precursors. Here we demonstrated that HMOX1 inhibits differentiation of myoblasts...

Questions

Question (1)
Question
Hello, does anybody know if there is any commercially available hyperlipemic serum for cell culture? It would be rather easier to obtain (and presumably more standardised) than serum from WHHL rabbits or rats/rabbits on high fat diet. I would like to check the effect of such serum on the MSC in vitro differentiation. There are lipid supplements available (eg. from Sigma) but they do not represent the whole repertoire of lipids and lipoproteins found in the sera of atherosclerotic patients. 

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