Secretory factors

Well, my curiosities on the stem-cell niche, their locations and their interconnecting functions etc are just ignited me to look are there any ‘secretory factors’ play role for this part. Indeed.. significantly there are some ‘secretory factors’ which play important role in the disorders of stem-cell niche.

References: (from top to below)

For picture 1:

Please click here for complete paper from David T. Scadden

For pictures 2, 3 and 4:

Please click here for complete paper from Michael L. Cher, etal

any opinions?

thought provoking glossaries and reference pitures

Today while started to read some articles about stem-cell nice interestingly I came across to read some elegant, thought provoking glossaries, from the team Rosandra Kaplan

Here are those:

Osteoblastic niche*: is also referred to as endosteal niche, located within the Bone Marrow that regulates stem-cell cycling and promotes quiescence. This niche is also associated with the vascular niche.

Vascular niche: a second niche for Haematopoietic Stem Cells (HSC)within the Bone Marrow. This niche is also associated with the Osteoblasic niche and their cellular subsequent process. It is thought to be where activated HSCs migrate to for proliferation and egress to the circulation.

Ischaemic niche*: site in the periphery, which direct site-specific recruitment of bone-marrow-derived cells (BMDCs) for tissue repair and new vessel formation.

Primary tumour niche: where BMDCs home to sites within tumours, where they are integral for angiogenic processes promoting growth and progression of malignancy.

Pre-metastatic niche: primary tumour directs early changes occurring within sites of future metastasis prior to the arrival of disseminating tumour cells, which lead to the formation of clusters of VEGF receptor 1+ Haematopoietic Progenitor Cells (HPC) and priming of the tissue to receive tumour cells.

- >secondary tumour or metastasis<-

Stem-cell niche: a physiologically defined microenvironment, both supportive and regulatory, that via cell–cell interaction can regulate balanced self renewal, differentiation and stem-cell quiescence.


-> BMDCs i.e., bone-marrow-derived cells is a term which is meant for both haematopoietic and endothelial bone-marrow-derived cells.


(*) both the ischaemic and the osteoblastic niche are thought to be act as physiological niche, apart from the general / normal stem-cell niche.

References: (from top to below)

For pictures 1 and 2:

Please click here for complete paper from David T. Scadden

For picture 3:

Please click here for complete paper from Rosandra N. Kaplan, etal

Seems like they’re interconnecting each other niche / functions by overlapping sets of molecules and pathways as well as due to influence of their surrounding factors.

what's your view?

finally ..it's happened..!

Until this date I have managed to do the posting with the help of using the portable USB disc (copying the PDF articles from university computer room and bringing them to home computer…reading and posting…). After a long time follow-ups and discussion, last week i got the internet connection at home computer. Though the speed are very dump and no fast (so its helping me to learn about how to optimise computer memory as well as way to gear up the internet speed,...), however, now I am getting some kinds of (pseudo) satisfaction that I am having internet connection at home computer, finally!!!

'spin-off' blog

Initially I posted here few nice web sites on the field of stem-cell biology, for quick reference purpose. after got feeling of ‘the work is not complete yet..’ just I continued and finally realised that there are lots of web sites are floating on difference places in both good condition as well as broken, un-updated form. As a result here is a new blog.

http://stemcellresources.blogspot.com/.

Please share your opinion!

List of rare diseases in stem-cells

The article ignited more enthusiasm to start to correlate with the field of stem-cell research i.e. whether the stem-cell community has focused any research on the rare diseases or not.

Though there are no direct research efforts on this area, however, some labs have focused on the rare diseases aspects while concentrating on stem-cell transplantation especially haematopoietic stem-cells and the associated lymphoma’s /leukemia’s

This is the list of diseases currently covered:


-Acute myeloid leukaemia (AML)
-FGFR1 tyrosine kinase gene – Myelo Proliferative Disorders (MPD)
-Fanconi anaemia
-Paroxysmal nocturnal hemoglobinuria (PNH)
-Childhood chronic myeloid leukemia (CML),
-Plasma cell leukemia
-Childhood myelodysplastic syndrome (MDS)
-Primary familial and congenital polycythaemia (PFCP)
-Infants primary hemophagocytic lymphohistiocytosis (HLH),
-Urothelium carcinomas
-Diamond Blackfan anemia (DBA)
-Primary mediastinal large B-cell non-Hodgkin's lymphoma
-Hepatosplenic T-cell lymphoma
-Aspergillus tracheobronchitis
-De novo erythroleukemia (EL)
-Granulocytic sarcoma (GS),
-Chronic granulocytic leukaemia (CGL)
-Primary cardiac myxosarcoma
-T-prolymphocytic leukemia (T-PLL)
-Congenital amegakaryocytic thrombocytopenia (CAMT)
-Thrombotic thrombocytopenic purpura (TTP)
-Juvenile systemic scleroderma (jSSc)
-Nasal natural killer (NK)/T-cell lymphoma
-The thrombocytopenia and absent radii (TAR)
-Rothmund-Thomson syndrome
-congenital erythropoietic porphyria
-Adults Acute lymphoblastic leukaemia
-Adult B/L3-acute lymphoblastic leukemia
- Juvenile chronic myelomonocytic leukemia (JCMMoL)
-Basophilic leukemia
-Amyloidosis
-juvenile metachromatic leukodystrophy
-T-cell post-transplant lymphoproliferative disorder/lymphoma.
- Rare pediatric cancer- Neuroblastoma
-Juvenile myelomonocytic leukemia (JMML)
-Anaplastic large-cell lymphoma, T-/null-cell type (ALCL),
-malignant infantile osteopetrosis (MIOP),
-hypereosinophilic syndrome
-Polycythemia vera (PV)
-Nephrogenic fibrosing dermopathy
-lymphocytic bronchiolitis
-Adolescent-onset and adult-onset esthesioneuroblastoma
-Gaucher disease
-Mastocytosis
-sphingolipid activator proteins (SAPs)


While referring these diseases I am getting 2 questions, irresistibly:

1) Whether Bone marrow-derived cells (BMDCs) have any role in rare- diseases?

2) Whether the stem-cell niches may varies between diseases to disease or just follow the same niche / micro environment which is followed by the common cancer/ or normal cellular microenvironment? The questions came after reading number of stem-cell niches.

Thanks for your discussion.

rare diseases

In a bookshop I got an attention on an unusual topic in an unusual magazine, recently. The name of the magazine is called Forbes and topic is ‘How Novartis aims to reap billions of dollars in sales by focusing on big drug makers ignored rare diseases’.


'....When rheumatologist Timothy Wright joined Novartis (nyse: NVS - news - people ) in 2004 his first project was to rejuvenate an experimental arthritis drug. It was viewed lukewarmly in the lab because a similar drug from Amgen (nasdaq: AMGN - news - people ) had been a commercial flop.

Wright proposed testing the drug in patients with a disease so rare that some of his superiors had never heard of it: Muckle-Wells syndrome. At most a couple of thousand patients worldwide have the inherited disorder, which causes recurring fevers, rashes, joint pain and kidney damage. University researchers had just pinpointed a source: a bad gene that causes the body to produce an oversupply of interleukin-1, an immune system protein.....'


Please follow the link, for the complete article


Tips for opening the page:

after the link has open, please select the first one which goes as follows:

Big Bucks - Forbes.com
For years big drugmakers ignored rare diseases. Now Novartis aims to reap billions of dollars in sales by focusing on them.members.forbes.com/forbes/2007/0521/060.html - 57k - Cached - Similar pages


You can click either the main link itself or the link, 'cached'!

SNO cells: a novel tool for isolation of cancer stem cells as well as for identification of state of pre-metastatic niche

The Haematopoietic stem cells (HSC) are a subset of bone marrow cells that are responsible for the constant renewal of blood as well as capacity to generate daughter stem cells through self-renewal process by interacting with their specific microenvironments known as HSC niche.

Within the HSC niche in adult bone marrow, there is highly reciprocal relationship between osteoblasts (care for osteogenesis) and haematopoietic cells (care for haematopoiesis). HSCs interact not only with osteoblasts and its subsets (named osteoblastic niche) but also with other stromal cells, including sinusoidal endothelial cells (also named vascular niche).These osteoblastic niche and the vascular niche likely play role of maintaining a quiescent HSC microenvironment as well as regulating stem cell proliferation, differentiation and mobilization, respectively (1).

Recently Jiwang Zhang etal demonstrated that bone surface lining specialised cells called mononuclear spindle – shaped N-cadherin+ CD45- osteoblastic (SNO) cells, a subset of osteoblasts, is function as a crucial component of the HSC niche to support the long-term quiescent Haematopoietic stem cells (HSCs) (2). The osteoblastic niche not only maintains the quiescent stem-cells, but also promotes cancer metastasis (3) as well as likely retains mutant stem cells (4). Interestingly the SNO cells supporting the HSCs something like cleft form by b-integrin and N-cadherin.

In parallel, Kaplan etal have demonstrated a novel concept of pre-metastatic niche where prior to the arrival of tumor cells, tumour cells instruct bone marrow cells to migrate to the appropriate organ site and forming a receptive environment (or a pre-metastatic niche) for the tumour cells to occupy(5).

While integrating the date of quiescent cells are not completely quiescent, as they will be engaged into the cell cycle to take part physiological or pathological process (6), express a different profile of targets (7) as well as possible role of unknown molecular signaling pathways and microenvironmental ‘education’ for future metastatic progression (8), seems like further experimentation strategy might support the SNO cells may not only act as a novel tool for isolation of cancer stem cells but could also play supportive role for beginning of future metastatic progression. Moreover, evaluating the role of metastatic based signalling / secreted factors on the SNO cell complex may also gives exciting opportunity towards develop novel therapeutic target.




Relevant references:


(i) Tong Yin etal The stem cell niches in bone J Clin Invest. 2006 May; 116(5):1195-201.


(2) Jiwang Zhang etal Identification of the haematopoietic stem cell niche and control of the niche size Nature. 2003 Oct 23; 425(6960):836-41


(3) Mei Zhang etal Stem cells in the etiology and treatment of cancer Curr Opin Genet Dev. 2006 Feb; 16(1):60-4. Epub 2005 Dec 27.


(4) Anne Wilson etal c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation Genes Dev. 2004 Nov 15; 18(22):2747-63


(5) Rosandra N. Kaplan etal VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche Nature. 2005 Dec 8; 438(7069):820-7.


(6) Hong-Bo Zhang etal Identification of label-retaining cells in nasopharyngeal epithelia and nasopharyngeal carcinoma tissues Histochem Cell Biol. 2007 Mar; 127(3):347-54. Epub 2006 Nov 30


(7) Axel Schulenburg etal Neoplastic stem cells: a novel therapeutic target in clinical oncology Cancer. 2006 Nov 15; 107(10):2512-20


(8) Bethan Psaila etal Priming the 'soil' for breast cancer metastasis: the pre-metastatic niche Breast Dis. 2006-2007; 26:65-74