Category: stem cell


Scientist uses bone cell progenitors derived from human embryonic stem cells to grow compact bone tissue in quantities large enough to repair centimeter-sized defects

Dr. Darja Marolt, an Investigator at The New York Stem Cell Foundation (NYSCF) Laboratory, is lead author on a study showing that human embryonic stem cells can be used to grow bone tissue grafts for use in research and potential therapeutic application. Dr. Marolt conducted this research as a post-doctoral NYSCF –Druckenmiller Fellow at Columbia University in the laboratory of Dr. Gordana VunjakNovakovic.

The study, published in the early online edition of Proceedings of the National Academy of Sciences during the week of May 14th, is the first example of using bone cell progenitors derived from human embryonic stem cells to grow compact bone tissue in quantities large enough to repair centimeter-sized defects. When implanted in mice and studied over time, the implanted bone tissue supported blood vessel ingrowth, and continued development of normal bone structure, without demonstrating any incidence of tumor growth.

Dr. Marolt’s work is a significant step forward in using pluripotent stem cells to repair and replace bone tissue in patients. Bone replacement therapies are relevant in treating patients with a variety of conditions, including wounded military personnel, patients with birth defects, or patients who have suffered other traumatic injury. Since conducting this work as proof of principle at Columbia University, Dr. Marolt has continued to build upon this research as an Investigator in the NYSCF Laboratory, developing bone grafts from induced pluripotent stem (iPS) cells. iPS cells are similar to embryonic stem cells in that they can also give rise to nearly any type of cell in the body, but iPS cells are produced from adult cells and as such are individualized to each patient. By using iPS cells rather than embryonic stem cells to engineer tissue, Dr. Marolt hopes to develop personalized bone grafts that will avoid immune rejection and other implant complications.

The New York Stem Cell Foundation has supported Dr. Marolt’s research throughout her career, first through a NYSCF – Druckenmiller Fellowship to fund her post-doctoral work at Columbia University, and now with a NYSCF – Helmsley Investigator Award at The New York Stem Cell Foundation Laboratory. “The continuity of funding provided by NYSCF has allowed me to continue my research uninterrupted, making progress more quickly than would have otherwise been possible,” Dr. Marolt said.

Provided by New York Stem Cell Foundation

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Article from Stem Cell blog

Betacellulin or BTC is a protein that was recently found to help boost brain regeneration in mice by stimulating the organ’s stem cells in order to multiply and form new nerve tissue. The findings that were released in the journal PNAS, boldly claim that the BTC protein can enhance current and future regenerative therapies for dozens of conditions including strokes, traumatic brain injury and dementia.

Although the majority of nerve cells  in the human brain are first formed within the womb & also soon after birth.  The new brain enhancing neurons will then continue to be generated throughout an adults life. The neural stem cells tend to be housed inside the two small ‘niches’ inside the brain and will supply the neurons to the brains olfactory bulb. The olfactory bilb is responsible for the sense of smell, and the hippocampus, is involved in forming memories and learning abilities.

According to the Stem Cell Blog The niches produce a range of signals that control how fast the originate cells divide and also the type of cell these people become. Stem cells in these areas usually produce neurons, however in brain injury cases such as strokes they tend to produce more so-called glial cells, leading to the development of scar tissue.

Dr Robin Badge lead researcher from the National Institute for Medical Research, said:

“The originate cell niches within the brain are not completely understood, but it appears that many factors act in concert to control the fate from the stem cells. We believe these factors are finely balanced to manage precisely the numbers of new neurons that are made to match demand in a number of normal circumstances.

“In trauma or disease, the actual stem cells possibly can’t cope with the increased demand, or they prioritise harm control at the expense of long-term repair. We hope that our new findings can add to the arsenal associated with exciting approaches coming out of stem cell biology that might eventually result in better treatments for damaged brains.”

The researchers analyzed the effects of BTC, that is produced within blood vessels that originate cell niches, around the rate of neuron development in mice. The reserachers found that the BTC proteins signal the stem cells and into dividing the tissues known as neuroblasts thus triggering their proliferation and regeneration.

When extra Betacellulin protein was given to the rodents, the researchers noticed a significant increase in both neuroblasts and  stem cells in the brains, leading to the formation of many new neurons. In start contrast to the group of mice that were given the BTC blocking antibody. The blockers suppressed the the production of new neurons in the rat brains.

Since the BTC protein leads to the production of new brain cell neurons instead of the glial cells, the BTC proteins is believed to eventually improve the overall effectiveness of the regenerative medical treatments that are aimed directly at helping repair the damage to our brains. Restorative healing using stem cells has the profound possibility to unlock new treatments for human illnesses that currently have no effective cures today.

The research is a critical step towards the goal of eventually moving well beyond simply replacing tissues and organs to the eventual exploitation of the intrinsic natural repair and regenerative potential of the human body. The work is still far from the clinical application as further experiments are necessary to explain the actions of the BTC protein in our brains.

Your hair or lack of will be the direct result of the lifelong tug-of-war in between activators that wake up, and cellular inhibitors that “calm” the stem cells in each and every hair follicle on your Body.  According to Dr Cheng-Ming Chuong of USC and his colleagues from Oxford University Dr Ruth Baker and Dr Philip Maini, the understanding of of “cellular automaton” model is crucial in helping describe the group behavior of hair follicles.The researchers discovered that every adult hair follicle can count only on their inherent growth-promoting signals, with out the assist of adjacent follicles within the macro-environment. In contrast to the growth promotion in Humans, the growth of rabbit and mice hair follicles will be dependent on signals from neighborly follicles.

The new cellular level automaton model consists of a normal grid of automation 1 hair follicle  with 4 distinct and functional cyclic stages. He also noted that Surrounding every automaton are 8 automata, which are the hair follicle’s neighbors.According to the stem cell blog website, Every automaton stage and modifications are based on guidelines that

Dr cheng ming chuong Cellular Level Modeling Predicts Hair Follicle Growth Via Stem CellsDr Cheng Ming Chuong

dictate if or not hair on human scalps or in animal’s fur coats will be caught up in large waves of growth known as the anagen phase, or stay within the telogen or resting phase. Under proper circumstances such as the winter season or a new physiological and/or developmental stage in an organism’s life like puberty for example, an amazing collective regeneration wave can sweep over your skin, activating all the hair stem cells in the individual follicles and even those in front of them, by the 10′s of thousands.

In other life stages, some individual hair follicles might even stay locked into the telogen stage by the inhibitors in their own macro-environment. The Inhibitor levels are carefully modulated in component by intradermal adipose tissue and also the central endocrine method. These numerous layers of manage produce a balance in between the inhibitory bone morphogenic protein or BMP. This is a signal that keeps hair stem cells in a calm quiescent state and later activating then with signals that wake them up.

The groundbreaking new information introduces a new method to treating androgenic alopecia, probably the most common type of hair loss or alopecia in most aging males: It may be simpler to obtain hair follicles expand them once more by enhancing their surrounding atmosphere, instead of the traditional stem cell treatments for hair loss.

FDA U.S. drug regulators have for the first time approved a therapy that uses cells of human blood from the placenta and the umbilical cord to treat people with blood-forming disorders or cancer.
The Food and Drug Administration (USA) on Thursday (Oct 10, 2011) licensed HEMACORD, manufactured by the New York Blood Center (NYBC), a therapy that contains self-recreating cells similar to stem cells from human cord blood. This therapy is known as hematopoietic progenitor cells-cord (HPC-C) cell therapy.
Those blood-forming types of cells, known as progenitor cells, are infused into patients and make their way to bone marrow, where they divide and mature. As they move into the bloodstream, they can help build new blood cells or restore their capacities, including immune function.
Hemacord is approved for use in blood-restoring stem cell transplants, which can use cells from three sources: cords, bone marrow and peripheral blood, the flowing blood that circulates through the body.
“We have been using cord blood for years,” said Dr. Machi Scaradavou, medical director of the NYBC’s National Cord Blood Program.” Recently, FDA decided that it needs to be licensed and this is the first cord blood product and stem cell product to be licensed.”
In 2009, the FDA guided manufacturers of such therapies to submit by Oct. 20 applications either for a license or for an approval as an investigational new drug. National Cord Blood Program is the first to get FDA’s nod, Scaradavou said.
The use of cord blood hematopoietic (blood-forming) progenitor cell therapy offers potentially life-saving treatment options,” said Dr. Karen Midthun, director of FDA’s Center for Biologics Evaluation and Research, in a statement.
Source:

Harvesting human adipose tissue-derived adult stem cells: resection versus liposuction.

Source

Department of Dermatology, Regensburg University Hospital, Regensburg, Germany.

Abstract

BACKGROUND:

Adipose tissue is an abundant source of mesenchymal stem cells (MSC), which can be used for tissue-engineering purposes. The aim of our study was to determine the more suitable procedure, surgical resection or liposuction, for harvesting human adipose tissue-derived stem cells (hASC) with regard to viability, cell count and differentiation potential.

METHODS:

After harvesting hASC, trypan blue staining and cell counting were carried out. Subsequently, hASC were cultured, analyzed by fluorescence-activated cell sorting (FACS) and differentiated under adipogenic, osteogenic and chondrogenic conditions. Histologic and functional analyzes were performed at the end of the differentiation period.

RESULTS:

No significant difference was found with regard to the cell counts of hASC from liposuction and surgically resected material (P=0.086). The percentage of viable cells was significantly higher for liposuction aspirates than for resection material (P=0.002). No significant difference was found in the adipogenic differentiation potential (P=0.179). A significantly lower number of cultures obtained from liposuction material than from resection material could be differentiated into osteocytes (P=0.049) and chondrocytes (P=0.012).

DISCUSSION:

Even though some lineages from lipoaspirated hASC can not be differentiated as frequently as those from surgically resected material, liposuction may be superior for some tissue-engineering purposes, particularly because of the less invasive harvesting procedure, the higher percentage of viable cells and the fact that there is no significant difference between lipoaspirated and resected hASC with regard to adipogenic differentiation potential.

The materials currently used in soft tissue regeneration, which include collagen, hyaluronic acid, silicon, and other filler materials, have several disadvantages such as high cost, immunogenicity/allergenicity, and the risk of transmitting infectious diseases. Meanwhile, autologous fat grafts are more widely available; however, one limitation of this technique is the poor long-term graft retention in current clinical practice (Min et al., 2010). The transplanted fat grafts can lose volume over time due to tissue resorption that can result in the loss of 20-90% of the original graft volume (Cherubino et al., 2009). The ideal solution for soft tissue regeneration would promote the regeneration of vascularized adipose tissue to completely fill the defect volume (Brayfield et al., 2010).

Recently, Frerich et al. (2005) reported an in vitro co-culture model using human adipose stromal cells and human umbilical vein ECs, where perfused tubes formed capillary-like networks that sprouted from the central lumen wall. Kang et al. (2009) developed an in vitro 3D model of tissue regeneration in which human vascularized adipose tissue, human ASCs, and human umbilical vein ECs were co-cultured on 3D aqueous silk scaffolds. After two weeks of co-culture, continuous endothelial lumens formed. Furthermore, Min et al. (2010) demonstrated in an in vivo murine model that the transplantation of fat tissue with non-cultured ASCs improved long-term graft retention. Compared with transplanted fat tissue alone, fat tissue transplanted with non-cultured ASCs had a higher density of capillaries six and nine months after transplantation. The reasons for these successful results might be the pro-angiogenic growth factors secreted by ASCs, as described previously.

Wound healing might be interrupted by a variety of pathological conditions, such as diabetes, radiation and immunosuppression, resulting in refractory chronic wounds (Lorens et al., 2006). Growth factors involved in wound healing have been individually applied to the wound to promote wound healing in unfavorable conditions. However, the theoretical promise of this approach was unfulfilled due to the complex nature of wound healing, which involves a number of different growth factors (Ebrahimian et al., 2009; Brem et al., 2009). To achieve optimal results, all these growth factors should be applied continuously, as opposed to the intermittent applications of individual growth factors (Brem et al., 2009; Blanton et al., 2009).

ASCs secrete nearly all of the growth factors that take part in normal wound healing (Ebrahimian et al., 2009; Blanton et al., 2009; Kim et al., 2007; Rehman et al., 2004). After application, ASCs may remain viable at the wound site and secrete growth factors in a continuous and regulated manner in response to environmental cues, just as occurs in the natural wound healing process (Badillo et al., 2007). ASCs promote wound healing by increasing vessel density, granulation tissue thickness, and collagen deposition (Ebrahimian et al., 2009), and they also improve the cosmetic appearance of resultant scars (Blanton et al., 2009).

A ready blood supply is crucial for wound healing. VEGF secreted from ASCs induces the migration and proliferation of ECs, increasing the vascularity of the wound bed (Lorens et al., 2006; Rehman et al., 2004). It was both experimentally and clinically shown that the topical administration of ASCs to full-thickness radiated wounds increase the healing rate of the wound (Ebrahimian et al., 2009; Rigotti et al., 2007). Kim et al. (2007) demonstrated that ASCs stimulate fibroblast proliferation and migration and type I collagen secretion in an in vitro wound model. These findings suggest that ASCs may promote in vivo wound healing.

Musculoskeletal Regeneration

Current therapeutic approaches for muscle loss cannot restore muscle function effectively. ASCs can differentiate into chondrogenic, osteogenic, and myogenic cells in vitro, and thus could potentially be used to regenerate tissue in musculoskeletal system disorders (Zuk et al., 2001; Mizuno et al., 2002).

Muscle tissue contains muscle progenitor cells called satellite cells that lie underneath the basal lamina (Kim et al., 2006; Di Rocco et al., 2006; Mizuno et al., 2002). These cells can divide and fuse to repair or replace damaged fibers in response to acute muscle injury or in chronic degenerative myopathies (Kim et al., 2006; Mizuno et al., 2002). However, continuous muscle degeneration-regeneration cycles in chronic cases lead to a depletion of the satellite cell pool. Moreover, it is difficult to expand satellite cells in vitro and they rapidly undergo senescence (Di Rocco et al., 2006; Mizuno et al., 2002).

ASCs may provide an easily accessible and expandable alternative cell source for the cellular therapy of muscular disorders. ASCs were successfully differentiated into skeletal muscle cells and smooth muscle cells in vitro (Jeon et al., 2010; Mizuno et al., 2002; Di Rocco et al., 2006). Differentiated ASCs even exhibited a contractile function similar to that of smooth muscle cells in vivo (Rodríguez et al., 2006). ASCs have also shown a capacity for myogenic differentiation in vivo. Allogeneic ASCs injected intravenously or directly into the affected muscle could restore muscle function in a murine muscular dystrophy model without any signs of immune rejection (Di Rocco et al., 2006). In another study, poly lactic-co glycolic acid (PLGA) spheres attached to myogenically-induced ASCs were injected subcutaneously into athymic nude mice. Injected ASCs differentiated into muscle cells and regenerated into new muscular tissue (Kim et al., 2006). However, it is still unclear whether ASCs directly differentiate into myogenic lineage cells or whether they become incorporated into muscle fibers via cell fusion. It is likely that ASCs contain different subsets of cells capable of either function (Di Rocco et al., 2006).

ASCs can form osteoid in vitro and in vivo (Hattori et al., 2004). ASCs combined with biomaterials were successfully used to repair critical bone defects (Di Bella et al., 2008; Yoon et al., 2007). Moreover, ASCs secrete osteoinductive growth factors, which may potentially recruit host bone-forming cells and induce osteogenesis when implanted in vivo (Hao et al., 2010). ASCs genetically modified to secrete bone morphogenic protein-2 (BMP-2) may also be an effective method for enhancing bone healing (Peterson et al., 2005).

Use of ASCs in intervertebral disc regeneration has also been reported (Hoogendoorn et al., 2008). Other applications of ASCs in musculoskeletal system are periodontal tissue regeneration and tendon regeneration. Tobita et al. (2008) reported that implanted ASCs were differentiated into the periodontal tissues including alveolar bone, cementum, and periodontal ligament in a rat model. In addition, topical administration of ASCs to tendon repair sites in rabbits accelerated tendon repair and significantly increased tensile strength (Uysal et al., 2011).

To further study the proliferation and multi-differentiation potentials of adipose-derived stem cells (ADSCs), the cells were isolated with improved methods and their growth curves were achieved with cck-8. Surface protein expression was analyzed by flow cytometry to characterize the cell phenotype. The multi-lineage potential of ADSCs was testified by differentiating cells with adipogenic, chondrogenic, osteogenic, and myogenic inducers. The results showed that about 5 x 10(5) stem cells could be obtained from 400 to 600 mg adipose tissue. The ADSCs can be continuously cultured in vitro for up to 1 month without passage and they have several logarithmic growth phases during the culture period. Also, the flow cytometry analysis showed that ADSCs expressed high levels of stem cell-related antigens (CD13, CD29, CD44, CD105, and CD166), while did not express hematopoiesis-related antigens CD34 and CD45, and human leukocyte antigen HLA-DR was also negative. Moreover, stem cell-related transcription factors, Nanog, Oct-4, Sox-2, and Rex-1 were positively expressed in ADSCs. The expression of alkaline phosphatase (ALP) was detected in the early osteogenic induction and the calcified nodules were observed by von Kossa staining. Intracellular lipid droplets could be observed by Oil Red staining. Differentiated cardiomyocytes were observed by connexin43 fluorescent staining. In order to obtain more stem cells, we can subculture ADSCs every 14 days instead of the normal 5 days. ADSCs still keep strong proliferation ability, maintain their phenotypes, and have stronger multi-differentiation potential after 25 passages.

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