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Human Postnatal Dental Pulp Cells Co-Differentiate into Osteoblasts and Endotheliocytes: A Pivotal Synergy Leading to Adult Bone Tissue Formation

PRC/D/2007/Mar 15

Cell Death and Differentiation (2007) 14

R d'Aquino, M Sampaolesi, G Laino, G Pirozzi, A De Rosa and G Papaccio

Dipartimento di Discipline Odontostomatologiche, Ortodontiche e Chirurgiche, Universita` Secondo Ateneo di Napoli, Napoli, Italy; Dipartimento di Medicina Sperimentale, Sezione di Istologia ed Embriologia, Universita` Secondo Ateneo di Napoli, Napoli, Italy; DIBIT Dipartimentale San Raffaele Scientific Institute, Universita` Vita e Salute, Stem Cell Research Institute, Milan, Italy and UOS Dipartimentale, Diagnostica Molecolare, Analisi d'immagine e citometrı´a a flusso, Istituto Nazionale Tumori 'G. Pascale', Napoli, Italy

Stromal stem cells from human dental pulp (SBP-DPSCs) were used to study osteogenic differentiation in vitro and in vivo. We previously reported that SBP-DPSCs are multipotent stem cells able to differentiate into osteoblasts, which synthesize three dimensional woven bone tissue chips in vitro. In this study, we followed the temporal expression pattern of specific markers in SBP-DPSCs and found that, when differentiating into osteoblasts, they express, besides osteocalcin, also flk-1 (VEGF-R2). In addition, 30% of them expressed specific antigens for endothelial cells, including CD54, von-Willebrand (domain 1 and 2), CD31 (PECAM-1) and angiotensin-converting enzyme. Interestingly, we found endotheliocytes forming vessel walls, observing that stem cells synergically differentiate into osteoblasts and endotheliocytes, and that flk-1 exerts a pivotal role in coupling osteoblast and endotheliocyte differentiation. When either SBP-DPSCs or bone chips obtained in vitro were transplanted into immunocompromised rats, they generated a tissue structure with an integral blood supply similar to that of human adult bone; in fact, a large number of HLA-1 + vessels were observed either within the bone or surrounding it in a periosteal layer. This study provides direct evidence to suggest that osteogenesis and angiogenesis mediated by human SBP-DPSCs may be regulated by distinct mechanisms, leading to the organization of adult bone tissue after stem cell transplantion.

Cell Death and Differentiation (2007) 14,1162-1171.doi:10.1038/sj.cdd.4402121;published online 9 March 2007


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Human CD34+ Stem Cells Produce Bone Nodules in Vivo


Cell Prolif.2008, 41

A. Graziano, R. d'Aquino, G. Laino, A. Proto, M. T. Giuliano, G. Pirozzi, A. De Rosa, D. Di Napoli and G. Papaccio

Dipartimento di Medicina Sperimentale, Sezione Istologia ed Embriologia, TESLab, Secondo Ateneo di Napoli, Napoli, Italy, Dipartimento di Discipline Odontostomatologiche, Ortodontiche e Chirurgiche, Secondo Ateneo di Napoli, Napoli, Italy, Dipartimento di Chimica Università degli Studi di Salerno, Salerno, Italy, Dipartimento di Medicina Sperimentale, Sezione di Biotecnologie, Secondo Ateneo di Napoli, Napoli, Italy, Oncologia Sperimentale C-Immunologia, Istituto Nazionale Tumori, Napoli, Italy, and Centro di Biotecnologie, AORN Cardarelli, Napoli, Italy

Objectives: The aim of this study was to select and provide enough stem cells for quick transplantation in bone engineering procedures.

Materials and Methods: germ pulp, collected from 25 healthy subjects aged 13–20 years, were subjected to magnetic-activated cell sorting to select a CD34+ Stem cell population capable of differentiating into pre-osteoblasts. These cells were allowed to adhere to an absorbable polylactic–coglycolic acid scaffold for 30 min, without any prior expansion, and the CD34+ cell-colonized scaffolds were then transplanted into immunocompromised rats, subcutaneously.

Results: After 60 days, analysis of recovered transplants revealed that they were formed of nodules of bone, of the same dimensions as the original scaffold.

This study indicates that CD34+cells obtained from dental pulp can be used for engineering bone, without the need for prior culture expanding procedures. Using autologous stem cells, this schedule could be used to provide the basis for bone regenerative surgery, with limited sacrifice of tissue, low morbidity at the collection site, and significant reduction in time needed for clinical recovery.


Human Dental Pulp Stem Cells Improve Left Ventricular Function, Induce Angiogenesis, and Reduce Infarct Size in Rats with Acute Myocardial Infarction

PRC/D/2008/Mar 2



Unidad de Cardiorregeneracio´n, Centro de Investigacio´n Prı´ncipe Felipe, Valencia, Spain


Human dental pulp contains precursor cells termed dental pulp stem cells (DPSC) that show self-renewal and multilineage differentiation and also secrete multiple proangiogenic and antiapoptotic factors. To examine whether these cells could have therapeutic potential (currently under experimental research) in the repair of myocardial infarction (MI), DPSC were infected with a retrovirus encoding the green fluorescent protein (GFP) and expanded ex vivo. Seven days after induction of myocardial infarction by coronary artery ligation, 1.5 _ 106 GFP-DPSC were injected intramyocardially in nude rats. At 4 weeks, cell-treated animals showed an improvement in cardiac function, observed by percentage changes in anterior wall thickening left ventricular fractional area change, in parallel with a reduction in infarct size. No histologic evidence was seen of GFP+ endothelial cells, smooth muscle cells, or cardiac muscle cells within the infarct. However, angiogenesis was increased relative to control-treated animals. Taken together, these data suggest that DPSC could provide a novel alternative cell population for cardiac repair, at least in the setting of acute MI. STEM CELLS 2008;26:638–645


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Clinical Outcomes of xeno-free autologous cultivated limbal epithelial transplantation :a 10-year study

Virender S Sangwan , Sayan Basu, Geeta K Vemuganti , Kunjal Sejpal , Sandhya V subramaniam , Souvik Bandyopadhyay , Sannapaneni Krishnaiah , Subhash Gaddipai, Shubha Tiwari, Dorairajan Balasubramanian

September 2, 2011 as 10.1136/bjophthalmol-2011-300352

LV Prasad Eye

Institute Efficacy of xeno-free autologuous cell- based treatment of limbal stem cell deficiency. A completely epithilised , avascular and clinically stable coreneal surface was seen in 142 of 200(71%) eyes at a mean follow-up of 3 + or – 1.6(range :1-7.6)years. Over the last two decades the surgical techniques has evolved from direct limbal transplantation to transplantation of ex vivo cultivated limbal epithelical cells, limbal cultivation may involve use of xenogenic tissue , associated with the risk of transmission of known or unknown infections to the transplant recipient of murine feeder cells, fetal bovine serum(FBS) or animal-derived growth factors. We report the long term survival, visual benefit and complications of transplantation of autologous limbal epithelial cells.


Stem cells in clinical practice: applications and warnings

Lodi et al. Journal of Experimental & Clinical Cancer Research 2011, 30:9

Daniele Lodi1 , Tommaso lannitti2*, Beniamno Palmieri3

A cell polarizes itself, so that cell-fate determinant molecules are specifically localized on one side. After that, the mitotic spindle aligns itself perpendicular to the axis polarity. End of the process two different cells are obtained [5-7]. Promising results have been described in disorders, such as diabetes [273] and neurodegenerative diseases [274, 275], where SCs graft can reestablish one or more deficit cellular lineages and, generally, a healthy state. Notably, many clinical studies have underlined the immunomodulatory effect of SCs in autoimmune diseases, such as multiple sclerosis [275], organ transplants [276] and in uncontrolled immune-inflammatory reactions [277-279].


Cardiovascular Applications of Stem Cell Therapy

Soheil Sadri1 , Ramesh Mazhari2, Maziar Sadri2, Nahal Konjedi1, and Palak Shah2*

Sadri et al.. J Stem Cell Res Ther 2011. S1

The prospect of cell-based therapies for cardiovascular disease has led to excitement within the scientific community as cardiovascular disease continues to be the leading cause of death worldwide. There is a growing body of evidence from both the basic sciences as well as through translational studies that prove the ability of stem cells to improve left ventricular function.


Mesenchymal stem cell-based therapies in regenerative medicine: application in rheumatology

Marie Maumus 1.2, David Guerit 1.2 , Karine Toupet 1.2, Christan Jorgensen 1.2.3 and Daniele Noel*1.2.4

Maumus et al. Stem Cell Research & Therapy 2011, 2:14

Growing knowledge on the biology of mesenchymal stem cells (MSCs) has provided new insights into their potential (currently under experimental research) clinical applications, particularly for rheumatologic disorders. Historically, their potential to differentiate into cells of the bone and cartilage lineages has led to a variety of experimental strategies to investigate whether MSCs also display immunosuppressive properties, which have prompted research on their capacity to suppress local inflammation and tissue damage in a variety of inflammatory autoimmune diseases and, in particular, in rheumatoid arthritis. Currently, an emerging field of research comes from the possibility that these cells, through their trophic/regenerative potential (currently under experimental research), may also influence the course of chronic degenerative disorders and prevent cartilage degradation in osteoarthritis.


Human Dental Pulp Stem Cells Hook into Biocoral Scaffold Forming an Engineered Biocomplex

Carlo Mango1', Francesca Paino2', Riccardo d' Aquino2 , Alfredo De Rosa3 , Giovanna lezzi4 , Adriano

Piattello4, Luigi Laino3, Thimios Mitsiadis5 , Vincenzo Desiderio2 , Francesco Mangano1, Gianpalolo

Papaccio2*, Virginia Tirino2

The aim of this study was to evaluate the behavior of human Dental Pulp Stem Cells (DPSCs), as well as human osteoblasts, when challenged on a Biocoral scaffold, which is a porous natural hydroxyapatite. For this purpose, human DPSCs were seeded onto a three-dimensional (3D) Biocoral Scaffold or on flask surface (control). Either normal or rotative (3D) cultures were performed. Scanning electron microscopic analyses, at 8, 24 and 48 h of culture showed that cells did not adhere on the external surface, but moved into the cavities inside the Biocoral structure. After 7, 15 and 30 days of culture, morphological and molecular analyses suggested that the Biocoral Structure. After 7, 15 and 30 days of culture, morphological and molecular analyses suggested that the Biocoral scaffold leads DPSCs to hook into the cavities where there cells quickly start to secrete the extra cellular matrix (ECM) and differentiate into osteoblasts. Controls human osteoblasts also moved into the internal cavities where they secreted the ECM. Histological sections revealed a diffuse bone formation inside the Biocoral samples seeded with DPSCs or human osteoblasts, where the original scaffold and the new secreted biomaterial were completely integrated and cells were found within the remaining cavities. In addition, RT-PCR analyses showed a significant increase of osteoblasts-related gene expression and above all, of those genes highly expressed in mineralized tissues, including osteocalcin, OPN and BSP. Furthermore, the effects on the interaction between osteogenesis and angiogenesis were observed and substantiated by ELISA assays. Taken together, our results provide clear evidence that DPSCs differentiated into osteoblasts, forming a biocomplex made of Biocoral, ECM and differentiated cells.


Dental Pulp Stem Cells and Tissue Engineering Strategies for Clinical Application on Odontoiatric Field

Zavan Barbara et al. University of Padova Italy

The dental pulp plays a major role in tooth regeneration after injury, participating process called reparative dentinogenesis.


Human dental pulp stem cell is a promising autologous seed cell for bone tissue engineering

LI Jing-hui, LIU Da-yong, ZHANG Fang-ming, WANG Fan, ZHANG Wen-kui and ZHANG Zhen-ting

Chin Med J 2011;124(23):4022-4028

In vitro studies revealed that hDPSCs do possess osteogenic differentiation potential .In vivo studies revealed that hDPSCs seeded on gelatin scaffolds can form bone structure in heterotopic sites of nude mice.

These findings suggested that hDPSCs may be valuable as seed cells for bone tissue engineering .As a special stem cell source ,hDPSCs may be blaze a new path for bone tissue engineering.


Odontogenic Differentiation of Human Dental pulp stem cells stimulated by the Calcium Phosphate Porous Granules

Sunyoung Nam, Jong-Eun Won, Cheol-Hwan Kim, and Hae –Won Kim

Effects of three-dimensional (3D) calcium phosphate (Cap) porous granules on the growth and odontogenic diffentiation of human dental pulp stem cells (hDPSCs) were examined for dental tissue engineering .hDPSCs isolated from human dental pulps were cultured for 3-4 passages, and populated on porous granules .Cell growth on the culture dish showed on ongoing increase for up to 21 days, whereas the growth on the 3D granules decreased after 14 days. This reduction in proliferative potential on the 3D granules was more conspicuous under the osteogenic medium conditions, indicating that the 3D granules may alkaline phosphatase activity, up-regulation of odontoblast- specific genes, including dentin sialosphosprotein (DSPP) and dentin matrix protein 1(DMPI) by quantitative polymerase chain reaction , and greater level of dentin sialoprotein synthesis by western blot. Moreover, the cellular mineralization, as assessed by Alizarin red S and calcium quantification, was significantly higher in the 3D CaP granules than in the culture dish. Taken all, the 3D CaP porous granules should be useful for dental tissue engineering in combination with hDPSCs by providing favorable 3D substrate conditions for cell growth and odontogenic development.


Stem cell-based treatments for Type 1 diabetes mellitus:

bone marrow, embryonic, hepatic, pancreatic and induced pluripotent stem cells

K. J. Godfrey1, B. Mathew1, J. C. Bulman1 , O. Shah1 , S. Clement2 and G. l. Gallicano3

Type I diabetes mellitus-Characterized by the permanent destruction of insulin-secreting β-cells-is responsive to cell-based treatment that replace lost β-cell populations. The current gold standard of pancreas transplantation provides only temporary independence from exogenous insulin and is fraught with complications, including increased mortality. Stem cells offer a number of theoretical advantages over current therapies. Our review will focus on the development of treatments involving tissue stem cells from bone marrow, liver and pancreatic cells, as well as the potential (currently under experimental research) use of embryonic and included pluripotent stem cells for Type 1 diabetes therapy. These cells have been demonstrated to increase endogenous insulin production, while partially mitigating the autoimmune destruction newly formed β-cells.

Diabet. Med. 29, 14-23 (2012)


Sinus Lift Augmentation Using Autologous Pulp Stem Cells: Case Report of Bone Density Evaluation

CAP/D/2011/Sep 1



Don Orione Hospital, Bergamo, Italy
(Applied Medical Imaging Research Group), Milan, Italy
Department of D.M.C.C.,Section of Maxillofacial and Plastic Surgery, University of Ferrara, Ferrara, Italy

Bone augmentation to reconstruct atrophic jaws provides the base for sufficient functional and aesthetic implant-supported oral rehabilitation. Although autografts are the standard procedure for bone grafting, the use of bone regeneration by means of dental pulp stem cell is an alternative that open a new era in this field. In March 2010, at the Department of Oral Surgery, Don Orione Hospital, Bergamo, Italy, one patient undergo to sinus lift elevation with pulp stem cells gentle poured onto collagen sponge. A CT scan control was performed after 4 month and DICOM data were processed with medical imaging software which gives the possibility to use a virtual probe to extract the bone density. Pearson's chi-square test was used to investigate difference in bone density (i.e. BD) between native and newly formed bone. BD in newly formed bone is about the double of native bone. This report demonstrated that stem cells derived from dental pulp poured onto collagen sponge is a useful method for bone regeneration in atrophic maxilla.


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Therapeutics of stem cells in periodontal regeneration

Journal of Natural Science , Biology and Medicine , Jan 2011, Vol 2, Issue 1

Rajiv Saini et al

The structure and composition of the periodontium are affected in many acquired and hentable diseases and the most significant among these is periodontal diseases .periodontal regeneration is considered to be organically promising but clinically capricious. The principal requirements for tissue engineering are incorporation of appropriate numbers of responsive progenitor cells and the presence of bioactive levels of regulatory signals within an appropriate extracellular matrix or carrier construct. Stem tissues that are damaged And recent progress in stem cells research and in tissue engineering promises nowel prospects for therapeutic strategies for the replacement of a diseased or damaged tooth.


Intravenous Mesenchymal Stem Cells Prevented Rejection of Allogeneic Corneal Transplants by Aborting the Early Inflammatory Response

Molecular Therapy, (28 August 2012)|doi:10.1038/mt.2012.165

Joo Youn Oh, Ryang Hwa Lee, Ah Young Ko, Gavin W Roddy and Darwin J Prockop

Mesenchymal stem/progenitor cells (MSCs) were reported to enhance the survival of cellular and organ transplants. However, their mode of action was not established. We here used a mouse model of corneal allotransplantation and demonstrated that peri-transplant intravenous (i.v.) infusion of human MSCs (hMSCs) decreased the early surgically induced inflammation and reduced the activation of antigenpresenting cells (APCs) in the cornea and draining lymph nodes (DLNs). Subsequently, immune rejection was decreased , and allograft survival was prolonged. Quantitative assays for human GAPDH revealed that 10 hMSCs out of 1 x 106 injected cells were recovered in the cornea 10 hours to 28 days after i.v. infusion. Most of hMSCs were trapped in lungs where they were activated to increase expression of the gene for a multifunctional anti-inflammatory protein tumor necrosis factor-α stimulated gene/protein 6 (TSG-6). I.V. hMSCs with a knockdown of TSG-6 did not suppress the early inflammation and failed to prolong the allograft survival. Also, i.v. infusion of recombinant TSG-6 reproduced the effects of hMSCs. Results suggest that hMSCs improve the survival of corneal allografts without engraftment and primarily by secreting TSG-6 that acts by aborting early inflammatory responses. The same mechanism may explain previous reports that MSCs decrease rejection of other organ transplants.


High-purity hepatic differentiated from dental pulp stem cells in serum-free medium

J Endod 2012 Apr;38(4):475-80. Epub 2012 Jan28

INTRODUCTION: We have previously differentiated hepatocyte like cells from deciduoud tooth pulp stem and extracted third molar pulp stem cells with a protocol that used fetal bovine serum, but it showed high contaminations of nondifferentiated cells. Both the lower purity of hepatically differentiated cells and usage of serum are obstacles for applications of cell therapy or regenerative medicine. Objective of this study was to investigate the capacity for and purity of hepatocyte-like differentiation of CD 117-positive dental pulp stem cells without serum.

METHODS: Mesenchymal cells from human deciduous and extracted third molar pulp were isolated and expanded in vitro. We separated D117-position cells by using a magnetic-activated cell sorter. The cells were characterized immunofluorescently by using known stem cell markers. For hepatic differentiation, the media were supplemented with hepatic growth factor, insulin transferring-selenium-x, dexamethasone, and oncostatin M. Expression of hepatic markers alpha fetoprotein, albumin, hepatic nuclear factor-4 alpha, insulin-like growth factor-1, and carbamoyl phosphate synthetase was examined immunoflurescently after differentiation. The amount of differentiated cells was assessed by using flow cytometry. Glycogen storage and area concentration in the medium were defined.

RESULTS: Both cell cultures demonstrated a number of cells positive for all tested hepatic markers after differentiation,ie, albumin-positive cells were almost 90% of differentiated deciduous pulp cells. The concentration of urea in the media increased significantly after differentiation. Significant amount of cytoplasmic glycogen storage was found in the cells.

CONCLUSIONS: Without serum both cell types differentiated into high-purity hepatocyte-like cells. These cells offer a source for hepatocypte lineage differentiation for transplantation in the future.


Stem Cells in Regenerative Endodontics: A Review

Parul Mehta

Regenerative Endodontics is expected to become the next big treatment revolution. It is the creation and delivery of tissues to replace a diseased, missing and traumatized pulp dentin complex, in addition to tooth supporting tissues. It employs dental stem cells for this which is especially important because they are a type of mesenchymal stem cells that produce more neurotrophic factors than other cell types. These cells have demonstrated the ability to protect and repair neural tissue in diseases like spinal cord injury and stroke and hence can also be used for development of treatment solutions for such diseases. Dental stem cells are also easy to procure and preserve for use in future therapies.



Prespectives on Mesenchymal Stem Cell: Tissue Repair, Immune Modulation, and Tumor Homing

Arch Pharm Res Vo 35, No,2 201-211, 2012
DOT 10.1007 / s 12272-012-0201-0

Hyun Sook Hong, Yeong Hoon Kim, Youngsook Son

Mesenchymal stem cells (MSCs) or MSC – Like cells have been identified in a variety of different tissues that share molecular expression profiles and biological functions but also retain a unique differentiation preference depending on their tissue origins. MSCs play beneficial roles in the healing of damaged tissue by directly differentiating to many different resident cell types and / or by secreting several trophic factors that aid tissue repair. Aside from MSCs reparative stem cell function, they drive immune responses toward immunosuppression and anti - inflammation . This novel function of MSCs opens up new avenues for clinical development of MSC immune - therapeutics to treat uncontrollable, life threatening, severe , chronic inflammation and autoimmune disease.

MSCs or MSC – like cells, even though their tissue origins are different, are quite similar in expression of molecular markers and biological functions. MSCs are expected as reparative stem cell for a variety of tissue injuries or disease by differentiating to many different types of resident tissue cells. More frequently, life threatening steroid refractory immune rejection, and autoimmune syndrome, MSCs other novel function, an immune modulating effect, is adopted for the therapeutic rationale. However, in certain tumor setting, MSCs immune modulatory function, in combination with their tumor homing preference, may provide a reason for their causing unwanted tumor progression. This tumor homing capacity of MSCs can be strategically utilized as a novel tumor – targeting anticancer therapeutic. In conclusion, recent progress in MSCs therapeutics promises benefits for numerous uncontrolled diseases that cannot be met by conventional medication. Also their possible risk for the progression of tumors was uncovered. Therefore, MSC therapeutics can be advantageously developed as a specific tumor – targeting delivery vehicle.



Journal of Bone & Joint Surgery, British Volume
J Bone Joint Surg Br 2012 vol, 94-B no. SUPP XXXVI 43

NAL-Hazaimeh, J Beattle, M Duggal and XB Yang


Angiogenesis and the ability to provide appropriate vascular supply are crucial for skeletal tissue engineering. The aim of this study was to investigate the anglogenic potential (currently under experimental research) of human dental pulp stromal cells (HDPSCs) and stro-1 positive populations as well as their role in tissue regeneration ( the clinical reality).

HDPSC were isolated from the pulp tissue of human permanent teeth by collagenase digestion. STRO-1 positive cells were enriched using mono clonal anti STRO-1 and anti CD-45 PE conjugated anti bodies together with and fluorescence activated cell sorting (FACS). Cells isolated by FACS were grown to passage 4 and cultured as mono layers or on 3D matrigel scaffold in endothelial cell growth medium -2 (EGM_2) with/without 50ng/ml of vascular endothelial growth factor (VEGF). Cells cultured in alpha MEM supplemented with 10% FCS were used as controls. After 24, 48 and 72 hours anglogenic marker expression (CD31, CD34, vWF and VEGFR-2) was determined by qRT-PCR and immune-histo chemistry.

Using three different donors 0.5-1.5% of total HDPSCs population was characterized as STRO_1+/CD45- cells at each time point cells cultured as mono layer in EGM-2 with VEGF showed up regulation of CD31 and VEGFR-2 expression compared to the control group while expression of CD34 and vWF remained unaffected . however on matrigel, all four genes were up regulated to different extents. CD31 and VEGFR-2 were up regulated to a greater degree compared to CD34 and vWF. Changes in gene expression in both cell types were time dependent. Immune-histochemical staining confirmed that the HDPSCs cultured in th test group showed positive staining for the four angiogenic markers ( CD31, CD34, vWF and VEGFR-2) when grown in both mono layer and 3D matrigel culture compared to control cultures. When cultured on matrigel ( but not monolayer) for 7 days, HDPSC formed tube like structures in the VEGF treated group.

This indicates the potential (currently under experimental research) of use HDPSCs and their STRO-1 positive population for angiogenesis to enhance skeletal tissue repair and/or regeneration toward translational research for clinical benefit.


Mesenchyamal dental stem cells in regenerative dentistry

Journal section: Biomaterials and Bioengineering in Dentistry

Doi: 10. 4317 medoral 17925

Mesenchymal Dental Stem cells derived from teeth are easily accessible multipotent cells with the capacity to differentiate into distinct cell types. This new source of stem cells could be of benefit in cellular therapy and the eventual development of techniques for use in regenerative dentistry and degenerative diseases.


Role of mesenchymal stem cell therapy in Crohn's disease

Jignesh Dalal, Kimberly Gandy & Jos Domen
Pediatric Research (2012) 71, 445-451 doi: 10.1038/pr.2011.56
08 February 2012

Many trials of mesenchymal stem cells (MSCs) have been published in the past 5-6 y. MSCs inhibit T-cell alloreactivity in vitro by soluble factors and direct cell-to-cell contact. They are safe to infuse in humans with no acute toxicity and no ectopic tissue formation. Promising results of MSC infusion for graft-vs-host disease and fistulizing Crohn's disease (CD) have been published. Treatment of CD requires a comprehensive treatment approach to maintain Symptomatic control, improve health-related quality-of-life measures, and minimize complications from the disease. In this review, we will discuss the results of clinical trials using a novel treatment in the form of MSCs for treatment of CD and related complications. Success of these phase l, ll and lll trials have set the stage for usage of this novel treatment for children with CD.


The current and future Therapies of Bone Regeneration to Bone Repair Defects

International Journal of Dentistry
Volume 2012, Article ID 148261, 7 pages

Eijiro Jimi,1.2 Shizu Hirata , 3Kenji Osawa,1 Masamichi Terashita,4
Chiaki Kitamura,2.3 and Hidefumi Fukushima 1

Bone defects often result from tumour resection, congenital malformation, trauma, fractures, surgery, or periodontitis in dentistry. Although dental implants serve as an effective treatment to recover mouth function from teeth defects, many patients do not have the adequate bone volume to build an implant. The gold standard for the reconstruction of large bone defects in the use of autogeneous bone grafts. While autogeneous bone grafts is the most effective clinical method, surgical stress to the part of the bone being extracted and the quantity of extractable bone limit this method. Recently mesenchymal stem cell-based therapies have the potential (currently under experimental research) to provide an effective treatment of osseous defects.

Although regenerative medicine has been tried in various fields, there is much demand for regenerative medicine in dentistry, particularly in bone regeneration. Depending on the state of periodontitis or jaw resection, it might take more than 6 to 12 months for occlusal reconstitution. Thus, the development of an efficient and high-quality bone derivation method is necessary. Cell-based therapy pave the way to rejection-free regenerative treatment for bone defects.


Stem cell therapy in oral and maxillofacial region: An Overview

Journal of Oral and Maxillofacial Pathology
Vol 16 issue 1 Jan – apr 2012 58

Sunil PM, Manikandan R 1, Muthu MS2, Abraham S3

The advantages of stem cells from oral and maxillofacial region is that

1. Have high plasticity. 2. It can be cryopreserved for longer period (Ideal for stem cell banking). 3. It showed good interaction with scaffold and growth factors. 4. Stem cells transplantations can cause pathogen transmission and also need immunosuppression, so autologous stem cell source is the best option. Dental pulp stem cells will be better fitting tool due to easy surgical access, the very low morbidity of the anatomical site after the collection of the pulp.[17]


Human Dental Pulp-Derived Stem Cells Promote Locomotor Recovery after Complete Transection of the Rat Spinal Cord by Multiple Neuro-Regenerative Mechanisms

PRC/D/2012/Jan 1

Kiyoshi Sakai, Akihito Yamamoto

Department of Oral and Maxillofacial Surgery, Department of Biochemistry, and Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Spinal cord injury (SCI) often leads to persistent functional deficits due to loss of neurons and glia and to limited axonal regeneration after injury. Here we report that transplantation of human dental pulp stem cells into the completely transected adult rat spinal cord resulted in marked recovery of hind limb locomotor functions. Transplantation of human bone marrow stromal cells or skin-derived fibroblasts led to substantially less recovery of locomotor function. The human dental pulp stem cells exhibited three major neuroregenerative activities. First, they inhibited the SCI-induced apoptosis of neurons, astrocytes, and oligodendrocytes, which improved the preservation of neuronal filaments and myelin sheaths. Second, they promoted the regeneration of transected axons by directly inhibiting multiple axon growth inhibitors, including chondroitin sulfate proteoglycan and myelin-associated glycoprotein, via paracrine mechanisms. Last, they replaced lost cells by differentiating into mature oligodendrocytes under the extreme conditions of SCI. Our data demonstrate that tooth-derived stem cells may provide therapeutic benefits for treating SCI through both cell-autonomous and paracrine neuroregenerative activities.


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Banking Baby, Wisdom Teeth For Stem Cells Banking..

New York

June 8, 2005—Baby and wisdom teeth, along with jawbone and periodontal ligament, are non-controversial sources of stem cells that could be "banked" for future health needs, according to a National Institutes of Health researcher who spoke today at the American Dental Association's national media conference. Harvested from the pulp layer inside the teeth, jawbone and periodontal ligament, these stem cells may one day correct periodontal defects and cleft palate, and may help restore nerve cells lost in diseases such as Parkinson's, according to Pamela Gehron Robey, Ph.D., Chief, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research of the National Institutes of Health, Department of Health and Human Services. Stem cells have the potential to save injured teeth and grow jawbone.

Regenerating an entire tooth is on the horizon, and years from now, Dr. Robey said stem cells from teeth and jawbo- ne might be used to correct cleft palate, one of the most common birth defects, sparing children multiple surgeries. "As long as a cell has a nucleus, anything is possible," Dr. Robey states. In time, individuals may be able to bank their own stem cells from baby and wisdom teeth, similar to the way umbilical cord blood is stored. At present, commercial facilities to store stem cells from teeth are not available. According to Dr. Robey, the viability of stem cells derived from baby teeth is determined by when the tooth comes out. The longer a loose tooth is left in the mouth to fall out on its own, the less viable it is as a source of stem cells. As research in the field progresses, Dr. Robey hopes that stem cells from baby and wisdom teeth may one day restore nerve cells damaged by diseases such as Parkinson's Disease, one of the most common neurological disorders affecting the elderly.

"The stem cells from jawbone and teeth share a common origin with nerve tissue," Dr. Robey points out. "With the proper cues, researchers may be able to encourage them to form nerve-like tissue which may restore cells that make dopamine, but much more work is needed." Dopamine is a brain chemical that nerve cells need to properly function. To extract the stem cells from teeth, researchers can remove the periodontal ligament, drill into the tooth to remove the crown and then extract the pulp which is placed in an enzyme solution to release the stem cells. From jawbone, cells can be isolated by collecting marrow following a tooth extraction, for example, or by biopsy.

Therapeutic Application

Dental Stem Cells can Differentiate into...

This has Potential Benefit in..


Cardiac cells (heart cells)


Repair damage caused by Myocardial Infarction (Heart Attack)

Neurones (nerve cells)


Repair due to stroke or other degenerative diseases

Myocytes (muscle cells)


Repair loss due to crush-injuries or other degenerative diseases

Osteocytes (bone cells)


Repair fractures and other joint/bone diseases

Adipocytes (fat cells)


Restore fat loss

Chondrocytes (cartilage cells)


Repair of cartilage after injuries or other degenerative diseases such as Osteoarthritis

Dermal tissue (skin cells)


Assistance in Plastic Surgery applications


  • Mesenchymal stem cells help repair hearts damaged by heart attack -- in part by becoming heart cells themselves.
  • Autologous Mesenchymal Stem Cell Therapy Delays the Progression of Neurological Deficits in Patients With Multiple System Atrophy -May 2008
  • Mesenchymal Stem Cell Transplantation Accelerates Hearing Recovery through the Repair of Injured Cochlear Fibrocytes
  • Mesenchymal stem cells have shown to have a Therapeutic potential of in prostate cancer bone metastasis –
  • Clinical applications of human Mesenchymal Stem Cells are evolving rapidly with the aim to improve hematopoietic engraftment, expanding HSC, preventing graft-versus-host disease (GVHD), correcting inborn metabolic errors and delivering a variety of therapeutic genes into the cells.


Applications of mesenchymal stem cells in tissue engineering and regenerative medicine

Mesenchymal stem cells have been used to regenerate marrow microenvironment after myeloablative therapy.

The use of natural and synthetic biomaterials as carriers for mesenchymal stem cells delivery has shown increasing promise for orthopedic therapeutic applications, especially bone formation. Mesenchymal stem cells are ideal for treating arthritis and connective tissue ailments. When introduced into the infarcted heart, mesenchymal stem cells prevent deleterious remodeling and improve recovery. Number of reports have also indicated that these cells possess the capacity to trans-differentiate into epithelial cells and lineages derived from the neuro-ectoderm, and in addition, mesenchymal stem cells can migrate to the sites of injury, inflammation and to tumors. These properties of mesenchymal stem cells make them promising candidates for use in regenerative medicine and may also serve as efficient delivery vehicles in site-specific therapy.

Future Research on Mesenchymal Stem Cells

According to American Diabetes Association, mesenchymal stem cells can be the key to healing diabetic foot ulcers: Diabetic foot ulcers are the primary cause of hospital admissions for diabetics. Foot ulcers that heal improperly are at risk for infection, which can lead to amputation

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