Review
Bone marrow mononuclear cells and acute myocardial infarction

Samer Arnous1, Abdul Mozid1, John Martin1 and Anthony Mathur2*

* Corresponding author: Anthony Mathur a.mathur@qmul.ac.uk

Author Affiliations

1 Department of Cardiology, London Chest Hospital, Bonner Road, London E2 9JX, UK

2 Department of Cardiology, London Chest Hospital, Queen Mary University of London, Barts and the London NHS Trust, Bonner Road, London E2 9JX, UK

For all author emails, please log on.

Stem Cell Research & Therapy 2012, 3:2 doi:10.1186/scrt93

The electronic version of this article is the complete one and can be found online at: http://stemcellres.com/content/3/1/2

Published: 17 January 2012

© 2012 BioMed Central Ltd

Abstract

Stem cell transplantation is emerging as a potential therapy to treat heart diseases. Promising results from early animal studies led to an explosion of small, non-controlled clinical trials that created even further excitement by showing that stem cell transplantation improved left ventricular systolic function and enhanced remodelling. However, the specific mechanisms by which these cells improve heart function remain largely unknown. A large variety of cell types have been considered to possess the regenerative ability needed to repair the damaged heart. One of the most studied cell types is the bone marrow-derived mononuclear cells and these form the focus of this review. This review article aims to provide an overview of their use in the setting of acute myocardial infarction, the challenges it faces and the future of stem cell therapy in heart disease.
Introduction

Despite the recent advances in percutaneous intervention, drug and device therapy, patients with acute myocardial infarction (AMI) and resulting left ventricular impairment have 13% mortality at 1 year [1]. Following the loss of over one billion cardiomyocytes in a functionally significant MI, the overloaded surviving cardiomyocytes undergo abnormal remodelling, eventually leading to heart failure. This condition, a leading cause of death and disability in the developed world, is associated with 5-year mortality rates of up to 70% in symptomatic patients [2]. Current conventional therapies do not correct underlying defects in cardiac muscle cell number [3].

The only therapeutic option that currently addresses cardiomyocyte loss is heart transplantation. However, due to stringent selection criteria and chronic shortage of donor hearts, the vast majority of patients are deemed unsuitable or never receive a transplant. Therefore, preventing this progression post-MI is a major challenge requiring novel therapeutic strategies such as stem cell transplantation to improve the prognosis and quality of life for these patients.

The traditional view that the heart is a terminally differentiated organ has been challenged by the discovery of differentiation of stem cells into cardiomyocytes in animal and human hearts [4-7]. This in turn has led to the exciting possibility for regenerative therapy for cardiomyocyte loss after a MI. The demonstration of functional recovery of myocardium through cardiomyogenesis and neoangiogenesis in AMI in murine models by Orlic and colleagues [8] generated tremendous interest in the potential of bone marrow-derived stem cells. Since then, the cardiomyogenic ability of these cells has been challenged. However, studies continue to demonstrate improvement in cardiac function and reduction in infarct size. It should be noted that progenitor cells also contribute to cardiac repair by mechanisms beyond the growth of new cardiomyocytes and as such may offer an ‘indirect’ benefit.
Animal and human trials

The most promising and obvious cell type for the growth of new cardiomyocytes is the embryonic stem cell; however, considerable technical and ethical issues exist with these cells, which must be overcome before their successful use in humans. Adult stem cells are an attractive option to explore for transplantation as they are autologous, but their differentiation potential is more restricted than embryonic stem cells. Currently, the major sources of adult cells used for basic research and in clinical trials originate from the bone marrow. The bone marrow mononuclear subset is heterogeneous and comprises mesenchymal stem cells, haematopoietic progenitor cells and endothelial progenitor cells. The differentiation capacity of different populations of bone marrow-derived stem cells into cardiomyocytes has been studied intensively. The results are rather confusing and difficult to compare, since different isolation and identification methods have been used to determine the cell population studied. To date, only mesenchymal stem cells seem to form cardiomyocytes, and only a small percentage of this population will do so in vitro or in vivo. Pragmatically, the translation of the basic science into clinical research has followed a common pathway: injection of bone marrow-derived mononuclear cells (BMMNCs) as a source of stem cells into the heart. Table 1 provides a summary of clinical trials using BMMNCs in patients with acute MI.

Table 1. Clinical trials using autologous bone marrow mononuclear cells in patients with acute myocardial infarction
Trials with no sham bone marrow harvest or intracoronary re-infusion in the control group

In the first human trial, Strauer and colleagues [9] re-infused intracoronary BMMNCs 7 days after myocardial infarction (MI). The mean number of mononuclear cells was 2.8 × 107. There was a significant improvement in myocardial perfusion and a reduction in the infarct region in the cell therapy group. The Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI) investigators randomised patients into intracoronary infusion of BMMNCs or ex vivo expanded circulating progenitor cells 4 days after MI [10]. There was a significant improvement in global and regional left ventricular (LV) function in both groups and a beneficial effect on the post-infarction remodelling process manifest by a profound improvement in wall motion abnormalities in the infarct area and a significant reduction in end-systolic LV volume at 4 months post-MI. The LV ejection fraction (LVEF) further improved at 12 months, resulting in a total increase of 9.3% at 1 year [11]. Of interest, there was no difference between the two active treatment groups. The mean number of infused cells was 245 × 106, which contained haematopoietic progenitor, mesenchymal and stromal cells. However, a major limitation of both of these trials was the lack of a control group receiving sham bone marrow harvest or intracoronary re-infusion.

Another trial in which there was no sham procedure is the Autologous Stem-Cell Transplantation in Acute Myocardial Infarction (ASTAMI) trial, which included only patients with acute anterior MI. The intracoronary re-infusion of BMMNCs 4 to 8 days after infarction did not have a beneficial effect on LVEF compared to percutaneous coronary intervention (PCI) alone at 6 months [12]. This lack of beneficial effect may be explained by the different cell processing protocols used in this trial. Cell processing protocols may have a significant impact on the functional capacity of bone marrow-derived stem cells [13]. Comparison of different isolation protocols revealed a vastly reduced recovery of mononuclear cells and nullification of the neovascularisation capacity when the ASTAMI cell isolation and storage protocol was used [13].

The Bone Marrow Transfer to Enhance ST-Elevation Infarct Regeneration (BOOST) trial, a slightly larger trial, included 60 patients that were randomised to receive intracoronary BMMNCs or standard therapy 4.8 days after successful PCI following AMI. There was a significant improvement in global LVEF in the cell treatment group at 6 months without an effect on LV remodelling [14]. However, this improvement was not maintained at 18 months. The mean number of bone marrow cells that were infused contained 9.5 × 106 CD34+ and 3.6 × 106 haematopoietic colony-forming cells. The improvement in LVEF did not correlate with the number of CD34+ cells or haematopoietic colony forming cells. Again, a major limitation of the BOOST trial is that the control group did not undergo a sham bone marrow harvest or intracoronary infusion.

The first long-term study involving 62 patients who underwent intracoronary BMMNC transplantation 7 days post-AMI not only resulted in an early significant improvement in ejection fraction (EF) and infarct size, but there was also a significant reduction in mortality and improvement in exercise capacity compared to controls at 5 years [15].
Randomised controlled trials

The Transcatheter Transplantation of Stem Cells for Treatment of Acute Myocardial Infarction (TCT-STAMI) trial, which included a control group receiving a placebo infusion, showed a significant (approximately 5%) improvement in LVEF of patients receiving intracoronary BMMNCs at 6 months [16].

Intracoronary bone marrow derived progenitor cells in acute infarction (REPAIR-AMI), a large randomized double-blind controlled trial that included over 200 patients, showed an improvement in the primary endpoint in the treatment group that was an absolute change in global LVEF from baseline to 4 months, as measured by quantitative left ventricular angiography [17]. Furthermore, the pre-specified cumulative endpoint of death, MI, or revascularisation was significantly reduced, and this benefit was maintained at one year follow-up [18]. The mean increase in LVEF in the BMMNC group was 2.5% and there was an inverse relationship between the baseline EF and the degree of improvement. For example, patients with a baseline EF below the median value (48.9%) had an absolute increase in global EF that was three times higher than that in the placebo group. In contrast, the improvement in LVEF in patients with a baseline EF that was above the median value was non-significant (0.3%). The timing of cell infusion post-PCI also had an effect on the primary endpoint. Patients in whom the cells were infused ≥5 days post-PCI were the only ones who derived benefit.

By contrast, the LEUVEN-AMI study by Janssens and colleagues [19] showed that intracoronary re-infusion of BMMNCs within 24 hours of reperfusion was associated with a greater reduction in infarct size and improved regional systolic function, but no overall improvement in global left ventricular function compared to controls.
Trials that used two different cell populations

More recently, the Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) trial, which included patients with anterior MI, uniquely compared two cell types. Patients were randomized to receive intracoronary infusion of unselected (n = 80) or selected CD34+CXCR4+ (n = 80) BMMNCs, or to the control group (n = 40) [20]. Although patients in the treatment group had a 3% improvement in LVEF, this did not reach statistical significance. However, the primary endpoint analysis included 5 hours) may be more likely to have significant improvement of LVEF following the BMMNC infusion [20].

The timing of cell infusion may also play a role on the derived benefit. Although the REPAIR-AMI trial suggests that the enhanced improvement of the LVEF was confined to patients who were treated ≥5 days after primary PCI, the investigators of the HEBE and REGENT trials showed no interaction between the timing of cell infusion and derived benefit. The meta-analysis by Martin-Rendon and colleagues [22], however, showed that the benefit of stem cell therapy was even greater when the BMMNCs were infused >7 days after MI. The effect of timing on the beneficial effects of BMMNC administration is further supported by the study by Lai and colleagues [31] that showed that intracoronary BMMNC administration provided cardio-protection in a fashion similar to ishaemic preconditioning. This benefit was only seen when the myocardium had not been preconditioned by other means. An ongoing study at our centre, the REGENERATE-AMI (ClinicalTrial.gov NCT00765453), is designed to study the delivery of BMMNCs at very early time points (within 6 hours of PCI). The purpose of this design is to replicate the animal models where very early interventions lead to a significant (40%) improvement in cardiac function [8].

The dose of infused BMMNCs has varied between different trials with variable results. There appears to be a dose-dependent improvement in EF, with the benefit of BMMNCs only seen when doses higher than 108 are administered [22].
Direct (transdifferentiation) and indirect (paracrine and angiogenesis) effects of stem cells

To date, there is no direct clinical evidence that cellular cardiomyogenesis in fact occurs in the human heart after transplantation of progenitor cells, and over the past few years, various experiments using different types of stem cells have shown that 4 days after reperfusion (based on available evidence). Furthermore, given the seemingly small improvements that these trials have shown, the cost-effectiveness of cell therapy will also need to be addressed.

Two ongoing randomised controlled trials (TIME and late TIME studies) may help us understand whether the timing of cell administration plays an important role. The TIME study (Clinicaltrials.gov NCT00684021) is a trial designed to assess the effect of timing (3 versus 7 days) of BMMNC administration versus placebo in patients with acute MI. The LATE TIME study (Clinicaltrials.gov NCT00684060) will assess the effect of BMMNC administration 2 to 3 weeks after a MI.
Future cells

Animal and human studies have clearly shown that stem cell engraftment into the myocardium is associated with improvement in cardiac function; however, the quest for the optimal population of cells remains a challenge [85,86]. Embryonic stem cells are able to transform into cardiomyocytes and can replicate indefinitely, although ethical issues – their potential to form teratomas and the need for immunosuppressive therapy – have hindered their use in clinical trials. Furthermore, one of the major limitations of adult stem cells, including skeletal myoblasts and bone marrow-derived stem cells, is their limited ability to cross their lineage boundaries.

Fat tissue-derived multipotent stem cells [87], multi-potential cells from bone marrow or skeletal muscle [88,89], somatic stem cells from placental cord blood [90], and cardiac-resident progenitor cells [32,91] all show promising pre-clinical and some clinical applications.

Ultimately, cells that more closely resemble embryonic stem cells in their regenerative potential without the ethical issues provide an important future direction. A cell type that comes close, and is on the horizon of being tested for potential clinical application, is the inducible pluripotent stem cell (iPSC). iPSCs can be generated from adult human somatic cells by retroviral transduction [92], have similar differentiation potential and may provide an alternative to pluripotent embryonic stem cells.
The future of bone marrow stem cells

For the time being, it is important to establish whether the simple unfractionated bone marrow cell approach has clinical benefit, given the large number of studies that have been performed using this cell type without providing a clear answer. Meta-analysis suggests a positive effect on surrogate cardiac end-points in studies using BMMNCs to treat AMI. There is now a need to perform a large scale clinical trial using clinical hard end-points such as mortality to establish whether the positive effects seen on surrogate end-points can indeed translate to meaningful clinical benefits.
Abbreviations

AMI: acute myocardial infarction; ASTAMI: Autologous Stem-Cell Transplantation in Acute Myocardial Infarction; BMMNC: bone marrow-derived mononuclear cell; BOOST: Bone Marrow Transfer to Enhance ST-Elevation Infarct Regeneration; EF: ejection fraction; LV: left ventricular; LVEF: left ventricular ejection fraction; MI: myocardial infarction; PCI: percutaneous coronary intervention; REPAIR-AMI: Intracoronary bone marrow derived progenitor cells in acute infarction; SDF: stromal-cell-derived factor.
Competing interests

The authors have no relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.
Acknowledgements

This work forms part of the research themes contributing to the translational research portfolio of Barts and the London Cardiovascular Biomedical Research Unit, which is supported and funded by the National Institute of Health Research.
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© 2012 BioMed Central Ltd unless otherwise stated. Part of Springer Science+Business Media.

ArticleYong Zhao1*, Zhaoshun Jiang2, Tingbao Zhao3, Mingliang Ye4, Chengjin Hu5,
Zhaohui Yin2, Heng Li6, Ye Zhang7, Yalin Diao4, Yunxiang Li4, Yingjian Chen5,
Xiaoming Sun5, Mary Beth Fisk8, Randal Skidgel9, Mark Holterman10, Bellur
Prabhakar11, Theodore Mazzone1

Abstract
Background
Inability to control autoimmunity is the primary barrier to developing a cure for
type 1 diabetes (T1D). Evidence that human cord blood-derived multipotent stem
cells (CB-SCs) can control autoimmune responses by altering regulatory T cells
(Tregs) and human islet β cell-specific T cell clones offers promise for a new
approach to overcome the autoimmunity underlying T1D.
Methods
We developed a procedure for Stem Cell Educator therapy in which a patient’s
blood is circulated through a closed-loop system that separates lymphocytes
from the whole blood and briefly co-cultures them with adherent CB-SCs before
returning them to the patient’s circulation. In an open-label, phase1/phase 2
study, patients (n = 15) with T1D received one treatment with the Stem Cell
Educator. Median age was 29 years (range: 15 to 41), and median diabetic
history was 8 years (range: 1 to 21).
Results
Stem Cell Educator therapy was well tolerated in all participants with minimal
pain from two venipunctures and no adverse events. Stem Cell Educator therapy
can markedly improve C-peptide levels, reduce the median glycated hemoglobin
A1C (HbA1C) values, and decrease the median daily dose of insulin in patients
with some residual β cell function (n = 6) and patients with no residual pancreatic
islet β cell function (n = 6). Treatment also produced an increase in basal and
glucose-stimulated C-peptide levels through 40 weeks. However, participants in the Control Group (n = 3) did not exhibit significant change at any follow-up.
Individuals who received Stem Cell Educator therapy exhibited increased
expression of co-stimulating molecules (specifically, CD28 and ICOS), increases
in the number of CD4+CD25+Foxp3+ Tregs, and restoration of Th1/Th2/Th3
cytokine balance.
Conclusions
Stem Cell Educator therapy is safe, and in individuals with moderate or severe
T1D, a single treatment produces lasting improvement in metabolic control. Initial
results indicate Stem Cell Educator therapy reverses autoimmunity and promotes
regeneration of islet β cells. Successful immune modulation by CB-SCs and the
resulting clinical improvement in patient status may have important implications
for other autoimmune and inflammation-related diseases without the safety and
ethical concerns associated with conventional stem cell-based approaches.
Trial registration: ClinicalTrials.gov number, NCT01350219

El objetivo de la medicina regenerativa es la obtención de células que puedan reemplazar tejidos que han sido dañados por diversos procesos patológicos. En este campo, un claro ejemplo sería el de la Diabetes Mellitus de Tipo I, ya que se conoce con exactitud el tipo de células diana que han sido dañadas (las células ß del páncreas), así como su función y localización. En consecuencia, son diversas las investigaciones que se han centrado en conseguir un protocolo que permita obtener células productoras de insulina a partir de células madre de diversos orígenes.

El primer problema al que se enfrenta la investigación es el de seleccionar el tipo de células madre a utilizar. A priori, las células embrionarias podrían constituir una buena fuente debido a su capacidad totipotente (capacidad para formar todos los tipos de células), pero los problemas éticos así como las complicaciones técnicas derivados de su uso dificultan su obtención. Consecuentemente, se ha optado por recurrir a las células madre adultas de tejidos fetales, concretamente a las células madre procedentes de tejidos extraembrionarios como el cordón umbilical, el amnios y el líquido amniótico y, entre otros, la placenta. Esta opción presenta ventajas significativas con respeto a las “fuentes clásicas” de obtención de células adultas. Asimismo, presentan una pluripotencialidad (capacidad para formar varios tipos de células, pero no todos) más amplia que la de las células provenientes de tejidos adultos, así como la posibilidad de disponer de una muestra en abundancia y de forma totalmente inocua y sin riesgo para el donante.

“Debido a los crecientes y recientes avances científicos, las células madre provenientes de tejido de cordón se han situado en el centro de atención de la biomedicina al abrir una vía esperanzadora para el tratamiento de múltiples enfermedades como por ejemplo la diabetes tipo I”.

Ensayos clínicos prometedores

Uno de los ensayos clínicos en esta materia, el del equipo dirigido por el Dr. Kuo Ching Chao1, obtuvo células mesenquimales a partir de la Gelatina de Wharton (tejido gelatinoso del cordón umbilical) con el objetivo de reemplazar los islotes pancreáticos no funcionales. Para ello realizó un cultivo en un medio específico llamado NCM (Neural Conditioned Medium). El resultado mostró 4 estadios de diferenciación que fueron evaluados a través del estudio de la expresión de genes específicos de células ß pancreáticas, mostrando en uno de los estadios una producción significativa de insulina. En el estudio se inyectaron estas células diferenciadas a unas ratas a las que previamente se había inducido químicamente diabetes insulino-dependiente. Tan sólo tres días más tarde, las ratas comenzaron a controlar sus valores de azúcares en sangre y superaron con éxito los tests de tolerancia a la glucosa.

De forma similar, el equipo del Dr. Hwai-Shi Wang2, también empleó células mesenquimales obtenidas a partir de tejido de cordón umbilical para obtener células con capacidad secretora de insulina. En este caso, se estudió la producción de otro componente llamado Péptido C como medida de evaluación y las células fueron implantadas en ratones NOD (estirpe de ratones modificados genéticamente para desarrollar diabetes insulinodependiente). De este modo, se comprobó que estos ratones adquirían la capacidad de controlar sus valores de glucosa en sangre tras el implante de estas células diferenciadas.

Investigaciones de este tipo han permitido demostrar la posibilidad de extraer células humanas, de diferenciarlas ex vivo y de reimplantarlas en un organismo (inicialmente ratones) para corregir una patología. Asimismo, también cabe destacar que estos animales de experimentación no precisaron medicación inmunosupresora para evitar el rechazo al trasplante de células humanas (llamado xenotrasplante), lo que sugiere una baja capacidad inmunogénica de estas células.

Recientemente, un estudio del Dr. Bhandari3 y su equipo probó que la obtención de células productoras de insulina a partir de células mesenquimales de tejido de cordón se podía realizar de forma eficaz y más rápida que en otros estudios anteriores en los que se necesitaban al menos 4 fases de diferenciación y que suponían una demora de varias semanas. En esta última investigación se consiguió obtener células productoras de insulina que reaccionaban a la estimulación por glucosa, en tan sólo una semana.

“Un equipo de investigación dirigido por el Dr. Bhandari obtuvo recientemente células productoras de insulina que reaccionaban a la estimulación por glucosa, en tan sólo una semana”.

Debido a los crecientes y recientes avances científicos, las células madre provenientes de tejido de cordón se han situado en el centro de atención de la biomedicina al abrir una vía esperanzadora para el tratamiento de múltiples enfermedades como por ejemplo la diabetes tipo I. Sus ventajas en cuanto a su origen fetal (edad y pluripotencialidad) y su obtención (extracción inocua, indolora y sin riesgo) las sitúan como grandes candidatas para la medicina regenerativa. La conservación de una muestra de sangre y tejido del cordón umbilical constituye, actualmente, una oportunidad única y la manera más sencilla de disponer de una reserva de células madre cuyo enorme potencial de futuro sólo alcanzamos a imaginar.

——————————————————————————–

BIBLIOGRAFÍA RECOMENDADA

1. Chao KC, Chao KF, Fu YS, Liu SH (2008) “Islet- Like clusters derived from mesenchymal stem cells in Wharton’s Jelly of the human umbilical cord for transplantation to control type 1 diabetes” PLoS ONE 3(1): e1451. doi:10.1317/journal.pone.0001451

2. Hwai-Shi Wang, Jia-Fwu Shyu, Wen-Sheng Shen, Hsin-Chi Hsu, Torng-Chien Chi, Chie-Pein Chen, Seng- Wong Huang, Yi-Ming Shyr, Kam-Tsun Tang, Tien-Hua Chen (2010) “Transplantation of insulin-producing cells derived from umbilical cord stromal mesenchymal stem cells to treat NOD mice” Cell Transplantation, vol.20 pp. 455-466. doi: 10.3727/096368910X522270 E-ISSN 1555-3892

3. Dilli Ran Bhandari, Kwang-Won Seo, Bo Sun, Min-Soo Seo, Hyung-Sik Kim, Yoo-Jin Seo, Jurga Marcin, Nicolas Forraz, Helene Le Roy, Denner Larry, McGuckin Colin, Kyung-Sun Kang (2011) “The simplest method for in vitro ß-cell production from human adult stem cells” Differentiation, vol.82, issue 3, pp.144-152. doi:10.1016/j.diff.2011.06.003Differentiation, vol.82, issue 3, pp.144-152. doi:10.1016/j.diff.2011.06.003

BMC Medicine 2011, 9:136 doi:10.1186/1741-7015-9-136
Published: 22 December 2011
Yves Henrotin
Bone repair failure is a major complication of open fracture leading to nonuninon of broken bone extremities and movement at the fracture site. This results in an important disability for patients. The role played by the periosteum and bone marrow progenitors in bone repair is now well documented. In contrast, limited information is available on the role played by myogenic progenitor cells in bone repair. In a recent article published in BMC Musculoskeletal Disorders, Liu et al. have compared the presence of myogenic progenitor (-myo D lineage cells) in closed and open fracture. They showed that myogenic progenitors are present in open, but not closed fractures, suggesting that muscle satellite cells may colonize the fracture site in the absence of intact periosteum. Interestingly, these progenitors expressed sequentially a chondrogenic and, thereafter, an osteoblastic phenotype suggestive of a functional role in the repair process. This finding opens new perspectives for the research of orthopaedic surgical methods which could maximize myogenic progenitors access and mobilization to augment bone repair. Please see related article: http://www.biomedcentral.com/1471-2474/12/288

Thomas Ichim1, Neil H Riordan2, David F Stroncek3*
1MediStem Inc., San Diego, CA, USA, 2Aidan Foundation, Chandler, AZ, USA, and 3Department of
Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
*Corresponding author
DFS: dstroncek@cc.nih.gov
Abstract
In mid November the biopharma industry was shocked by the announcement from Geron that they
were ending work on embryonic stem cell research and therapy. For more than 10 years the public
image of all stem cell research has been equated with embryonic stem cells. Unfortunately, a
fundamentally important medical and financial fact was being ignored: embryonic stem cell therapy
extremely immature. In parallel to efforts in embryonic stem cell research and development, scientists
and physicians in the field of adult stem cells realized that the natural role of adult stem cells in the body
is to promote healing and to act like endogenous “repair cells” and, as a result, numerous companies
have entered the field of adult stem cell therapy with the goal of expanding numbers of adult stem cells
for administration to patients with various conditions. In contrast to embryonic stem cells, which are
extremely expensive and potentially dangerous, adult cell cells are inexpensive and have an excellent
safety record when used in humans. Many studies are now showing that adult stem cells are a practical,
patient-applicable, therapeutics that are very close to being available for incorporation into the practice
of medicine. These events signal the entrance of the field of stem cells into a new era: an era where
hype and misinformation no longer triumph over economic and medical realities.