scholarly journals HEMOPOIEITC SPLEEN COLONY STUDIES

1967 ◽  
Vol 125 (4) ◽  
pp. 703-720 ◽  
Author(s):  
J. L. Curry ◽  
J, J. Trentin ◽  
N. Wolf
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Morphological Differentiation ◽  
Erythroid Differentiation ◽  
Colony Growth ◽  
The Other ◽  
Colony Development ◽  
Undifferentiated Cells ◽  
Specific Stimulation ◽  
And Function

The polycythemic repression of erythropoiesis and the restoration of erythropoiesis by specific stimulation were studied in the spleen colony system in irradiated mice. 1. A 5 day period of erythropoietin stimulation (exogenous erythropoietin) or repression (polycythemia) of the bone marrow donor only, does not significantly alter the number or type of colonies formed by the transplanted marrow cells. 2. Erythropoietin stimulation did not alter the number or type of endogenous colonies formed in mice receiving 580 R. Erythropoietin repression (polycythemia) markedly reduced the growth but not the number of erythroid colonies, while not affecting the other types of colonies formed endogenously. 3. Erythropoietin stimulation of the irradiated recipient during colony growth did not alter the number or type of spleen colonies formed by transplanted marrow. Erythropoietin repression by polycythemia during colony growth completely suppressed the appearance of morphologically erythroid colonies without significantly altering the incidence of the other colony types. This effect of polycythemia was completely prevented by exogenous erythropoietin. Irradiated mice are therefore presumed to be secreting sufficient erythropoietin for maximal erythroid colony development. 4. The erythroid colonies suppressed by polycythemia were recognizable as microscopic foci of undifferentiated cells. Exposure of these foci to erythropoietin stimulation at different periods in their development was manifested by different degrees of growth and differentiation, from which it is apparent that erythropoietin stimulates not only morphological differentiation but also rapid mitosis. Retransplantation of either erythroid or of neutrophilic primary spleen colonies gave rise to both erythroid and neutrophilic secondary spleen colonies. The percentage of erythroid secondary colonies was slightly but significantly higher among the progeny of transplanted erythroid primary colonies than among the progeny of transplanted neutrophilic primary colonies. On the basis of these and other results, a working hypothesis is proposed for factors controlling the growth and differentiation of spleen colonies from transplanted bone marrow. It is postulated that most but perhaps not all spleen colony-forming units are pluripotent hemopoietic stem cells. It is further postulated that hemopoietic-inductive microenvironments (HIM) of different kinds exist in both the spleen and the bone marrow, and that these determine the differentiation of pluripotent stem cells into each of the lines of hemopoietic differentiation. Erythropoietin therefore may "induce" erythroid differentiation of only those stem cells under the influence of an erythroid HIM. Alternatively erythropoietin may act only as a growth and function stimulant of those stem cells that have been "induced" by an erythroid HIM into a state of erythropoietin responsiveness. In the latter case morphological differentiation presumably results from the functional activity stimulated by ESF.

scholarly journals Biological and microbiological interactions of Ti-35Nb-7Zr alloy and its basic elements on bone marrow stromal cells: good prospects for bone tissue engineering

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Daphne de Camargo Reis Mello ◽  
Lais Morandini Rodrigues ◽  
Fabia Zampieri D’Antola Mello ◽  
Thais Fernanda Gonçalves ◽  
Bento Ferreira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Differentiation ◽  
Stromal Cells ◽  
Biofilm Formation ◽  
Bone Marrow Stromal Cells ◽  
Pure Titanium ◽  
Marrow Stromal Cells ◽  
The Other ◽  
Cell Based Therapy

Abstract Background An effective biomaterial for bone replacement should have properties to avoid bacterial contamination and promote bone formation while inducing rapid cell differentiation simultaneously. Bone marrow stem cells are currently being investigated because of their known potential for differentiation in osteoblast lineage. This makes these cells a good option for stem cell-based therapy. We have aimed to analyze, in vitro, the potential of pure titanium (Ti), Ti-35Nb-7Zr alloy (A), niobium (Nb), and zirconia (Zr) to avoid the microorganisms S. aureus (S.a) and P. aeruginosa (P.a). Furthermore, our objective was to evaluate if the basic elements of Ti-35Nb-7Zr alloy have any influence on bone marrow stromal cells, the source of stem cells, and observe if these metals have properties to induce cell differentiation into osteoblasts. Methods Bone marrow stromal cells (BMSC) were obtained from mice femurs and cultured in osteogenic media without dexamethasone as an external source of cell differentiation. The samples were divided into Ti-35Nb-7Zr alloy (A), pure titanium (Ti), Nb (niobium), and Zr (zirconia) and were characterized by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). After predetermined periods, cell interaction, cytotoxicity, proliferation, and cell differentiation tests were performed. For monotypic biofilm formation, standardized suspensions (106 cells/ml) with the microorganisms S. aureus (S.a) and P. aeruginosa (P.a) were cultured for 24 h on the samples and submitted to an MTT test. Results All samples presented cell proliferation, growth, and spreading. All groups presented cell viability above 70%, but the alloy (A) showed better results, with statistical differences from Nb and Zr samples. Zr expressed higher ALP activity and was statistically different from the other groups (p < 0.05). In contrast, no statistical difference was observed between the samples as regards mineralization nodules. Lower biofilm formation of S.a and P.a. was observed on the Nb samples, with statistical differences from the other samples. Conclusion Our results suggest that the basic elements present in the alloy have osteoinductive characteristics, and Zr has a good influence on bone marrow stromal cell differentiation. We also believe that Nb has the best potential for reducing the formation of microbial biofilms.

Abstract 253: The Presence of Coronary Artery Disease Influences Number and Function of Stem Cells in the Bone Marrow

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Evelien Nollet ◽  
Dina De Bock ◽  
Inez R Rodrigus ◽  
Vicky Y Hoymans ◽  
Christiaan J Vrints ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Stem Cells ◽  
Bone Marrow ◽  
Renal Function ◽  
Stem Cell ◽  
Coronary Artery ◽  
Therapeutic Benefits ◽  
Migratory Capacity ◽  
Artery Disease ◽  
And Function

Purpose: Despite the observed therapeutic benefits of autologous bone marrow (BM)-derived stem cell transplantation in patients with ischemic heart disease, the efficacy of this approach could be hampered by BM dysfunction. We investigated whether BM cellularity and function is affected by coronary artery disease (CAD). Methods & Results: BM samples were obtained peri-operatively from 26 CAD patients, undergoing coronary artery bypass surgery (LVEF 54±16%), and 6 controls, undergoing mitral valve surgery (LVEF 50±12%; age 59±10yrs). CAD patients were stratified according to their Syntax score (mild ≤15, age 61±10yrs; and moderate CAD >15, age 63±8yrs; stratification based on median score), which is used to assess complexity of coronary lesions. In vitro functional analysis of isolated BM-derived mononuclear cells (BM-MNC) revealed a significant impairment of migratory capacity towards SDF-1α and VEGF in patients with moderate CAD (25.71±7.3%) compared to controls (33.82±8.3%; p=0.042) and patients with mild CAD (34.76±7.8%; p=0.007). Hematopoetic stem cells (HSC, CD45dimCD34+SSClow) were reduced in patients with moderate CAD (8178±5530 HSC/106 BM-MNC; p=0.014) and mild CAD (10655±5489 HSC/106 BM-MNC; p=0.054) compared to controls (16220±6126 HSC/106 BM-MNC). An inverse correlation was found between age and the number of granulocyte-macrophage colony forming units (r= −0.408; p=0.048), burst forming units erythroid (r= −0.458; p=0.028) and HSC (r=-0.356; p=0.046). Furthermore, our data revealed a relation between reduced renal function (CKD-EPI eGFR, 81.2±19 ml/min) and reduced number of HSC (r=0.480; p=0.011) and endothelial progenitor cells (EPC, CD45dimCD34+KDR+; r=0.522; p=0.008). Conclusions: Migratory capacity of BM-MNC and the number of HSC are reduced in patients with CAD, which is more pronounced in more complex CAD. In addition, age and renal function emerge as relevant determinants on BM function and stem cell populations. Therefore, these factors should be taken into account when assessing benefits of autologous stem cell therapy.

Human Primary CD271+/CD45−/CD146−/Low and CD271+/CD45−/CD146+ Bone Marrow Cells Are Developmentally Closely-Related Stroma Stem Cells with Similar Functional Properties but Different In-Situ Localization.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2594-2594 ◽  
Author(s):  
Ariane Tormin ◽  
Ou Li ◽  
Jan Claas Brune ◽  
Stuart Walsh ◽  
Mats Ehinger ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Functional Properties ◽  
Bone Marrow Cells ◽  
Human Bone ◽  
Reticular Cells ◽  
And Function ◽  
Cd146 Expression ◽  
Marrow Cells

Abstract Abstract 2594 Mesenchymal stem cells (MSC) are of central importance for the hematopoietic microenvironment. However, the exact contribution of specified MSC populations to bone marrow stroma anatomy and function is unknown. We have previously characterized the phenotype of primary human bone marrow MSC and found that all assayable CFU-F were highly and exclusively enriched not only in the lin−/CD271+/CD45−/CD146+ cell fraction, but also in lin−/CD271+/CD45−/CD146−/low cells. Both populations, regardless of CD146 expression, shared a similar phenotype and genotype and gave rise to typical cultured stroma cells. However, we observed that CD146 expression was up-regulated in normoxia and down-regulated in hypoxia, which correlated to in situ localization differences: CD146 co-expressing reticular cells were located in perivascular regions, whereas bone-lining MSC expressed CD271 alone (Tormin et al, Blood 2009, 114[22]:107). We now went on to further characterize the two populations with regard to in-situ localization and function. Multicolor confocal microscopy analysis of normal human bone marrow sections revealed that CD34+ hematopoietic stem/progenitor cells were located in close proximity to CD271+ MSC in perivascular as well as endosteal regions. Ongoing experiments address whether particular HSC subsets localize specifically with certain stroma stem cell populations. To further investigate possible functional differences between lin−/CD271+/CD45−/CD146+ and lin−/CD271+/CD45−/CD146-/low cells, FACS-sorted single cells were clonally expanded, loaded overnight on hydroxyapatite/tricalcium phosphate (HA/TCP) ceramic powder and transplanted s.c. into NOD-SCID mice. Eight weeks post transplantation, bone, adipocytes, fibroblastic tissue, and capillaries could be detected in both transplants. Orthotopic intrafemoral transplantations into irradiated NSG mice were performed with GFP-labeled MSC generated from either lin−/CD271+/CD45−/CD146-/low or lin−/CD271+/CD45−/CD146+ cells. After 8 weeks, GFP+ cells could be detected in the perivascular regions surrounding the endothelium of vessels, and as cells lining the surface of cortical and trabecular bone, surrounding adipocytes, or as reticular cells in the marrow space. Some of the bone-lining GFP+ MSC were found to express N-cadherin. Interestingly, this anatomical distribution is similar to the localization of primary MSC in human marrow in situ. No differences were observed between transplanted cells from lin−/CD271+/CD45−/CD146-/low MSC compared to lin−/CD271+/CD45−/CD146+ derived cells. Secondary colony-formation capacity was investigated by harvesting bone marrow cells 8 weeks post intrafemoral transplantation and plating them for CFU-F in standard MSC culture medium. GFP-positive fibroblastic colony growth was detected in the bone marrow of mice transplanted with lin−/CD271+/CD45−/CD146-/low as well as in the marrow of mice transplanted with lin−/CD271+/CD45−/CD146+ derived MSC. Taken together, our findings indicate that lin−/CD271+/CD45−/CD146-/low and lin−/CD271+/CD45−/CD146+ bone marrow cells are developmentally closely-related stroma stem cells with similar functional properties but different in-situ localization, which might be the first step towards a better characterization of the human hematopoietic microenvironment. Disclosures: No relevant conflicts of interest to declare.

Characterization of Hematopoietic Stem Cell Frequency and Function In Unexplained Anemia of the Elderly

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2047-2047
Author(s):  
Wendy Pang ◽  
Elizabeth Price ◽  
Irving L. Weissman ◽  
Stanley L. Schrier
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
In Vitro Culture ◽  
Progenitor Cells ◽  
The Elderly ◽  
Elderly Subjects ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
And Function

Abstract Abstract 2047 Anemia is both a highly prevalent and clinically important condition that causes significant morbidity and mortality in the elderly population. While anemia in the elderly can be attributed to a number of causes, approximately 30% of elderly subjects with anemia have no overt etiology and fall under the category of unexplained anemia of the elderly (UA). There is increasing evidence to suggest that changes in the frequency and/or function of hematopoietic stem and progenitor cells may contribute to the onset and pathophysiology of age-associated hematological conditions, such as UA. Hematopoietic stem cells (HSC) reside at the top of the hematopoietic hierarchy and can differentiate, via increasingly committed downstream progenitors, into all the mature cells of the hematopoietic system. Human myelo-erythroid development proceeds through a set of oligopotent progenitors: HSC give rise to multipotent progenitors (MPP), which give rise to common myeloid progenitors (CMP), which in turn give rise to granulocyte-macrophage progenitors (GMP) and megakaryocyte-erythrocyte progenitors (MEP). We use flow cytometry and in vitro culture of sorted human HSC (Lin-CD34+CD38-CD90+CD45RA-), MPP (Lin-CD34+CD38-CD90-CD45RA-), CMP (Lin-CD34+CD38+CD123+CD45RA-), GMP (Lin-CD34+CD38+CD123+CD45RA+), and MEP (Lin-CD34+CD38+CD123-CD45RA-) from hematologically normal young (23 samples; age 20–35) and elderly (11 samples; age 65+) and UA (5 samples; age 65+) bone marrow samples in order to characterize the changes in the distribution and function of hematopoietic stem and progenitor populations during the aging process and, in particular, in the development of UA. We found that UA patients contain higher frequencies of HSC compared to both elderly normal (1.5-fold; p<0.03) and young normal samples (2.8-fold; p<10-5). We also found increased frequencies of MPP from UA patients compared to MPP from elderly normal (2.6-fold; p<0.002) and young normal samples (5.8-fold; p<0.04). While we observed similar frequencies of CMP among the three groups, we found a notable trend suggesting decreased frequencies of GMP and corresponding increased frequencies of MEP in UA patients. Functionally, HSC from the three groups exhibit statistically insignificant differences in the efficiency of colony formation under the myeloid differentiation-promoting methylcellulose-based in vitro culture conditions; however, on average, HSC from elderly bone marrow samples, regardless of the presence or absence of anemia, tend to form fewer colonies in methylcellulose. Interestingly, HSC from UA patients produce more granulocyte-monocyte (CFU-GM) colonies and fewer erythroid (CFU-E and BFU-E) colonies, compared to HSC from normal samples (p<0.001). Similarly, CMP from UA patients, compared to normal CMP, yield skewed distributions of myeloid-erythroid colonies when plated in methylcellulose, significantly favoring production of CFU-GM colonies over CFU-E and BFU-E colonies (p<0.003). Additionally, MEP from UA patients form both CFU-E and BFU-E colonies in methylcellulose albeit at a significantly lower efficiency than MEP from normal bone marrow samples (p<0.01). This is the first study to examine the changes in hematopoietic stem and progenitor populations in UA patients. The changes in the distribution of hematopoietic stem and progenitor cells in UA patients indicate that the HSC and MPP populations, and possibly also the MEP population, expand in the context of anemia, potentially in response to homeostatic feedback mechanisms. Nevertheless, these expanded populations are functionally impaired in their ability to differentiate towards the erythroid lineage. Our data suggest that there are intrinsic defects in the HSC population of UA patients that lead to poor erythroid differentiation, which can be readily observed even in the earliest committed myelo-erythroid progenitors. We have generated gene expression profiling data from these purified hematopoietic stem and progenitor populations from UA patients to try to identify biological pathways and markers relevant to disease pathogenesis and potential therapeutic targets. Disclosures: Weissman: Amgen, Systemix, Stem cells Inc, Cellerant: Consultancy, Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Schrier:Celgene: Research Funding.

scholarly journals Osteoimmunology: Interactions of the Bone and Immune System

2008 ◽  
Vol 29 (4) ◽  
pp. 403-440 ◽  
Author(s):  
Joseph Lorenzo ◽  
Mark Horowitz ◽  
Yongwon Choi
Keyword(s):  
Bone Marrow ◽  
Immune System ◽  
Immune Cells ◽  
Bone Cells ◽  
The Other ◽  
Organ Systems ◽  
Health And Disease ◽  
The Many ◽  
And Function ◽  
Broad Overview

Abstract Bone and the immune system are both complex tissues that respectively regulate the skeleton and the body’s response to invading pathogens. It has now become clear that these organ systems often interact in their function. This is particularly true for the development of immune cells in the bone marrow and for the function of bone cells in health and disease. Because these two disciplines developed independently, investigators in each don’t always fully appreciate the significance that the other system has on the function of the tissue they are studying. This review is meant to provide a broad overview of the many ways that bone and immune cells interact so that a better understanding of the role that each plays in the development and function of the other can develop. It is hoped that an appreciation of the interactions of these two organ systems will lead to better therapeutics for diseases that affect either or both.

scholarly journals The separation of Antler Polypeptide and its effects on the proliferation and osteogenetic differentiation of Bone Marrow Mesenchymal Stem Cells

2020 ◽  
Author(s):  
Wang Ping ◽  
Sun Tie-Feng ◽  
Li Gang ◽  
Zhang Hui-Min ◽  
Liu Fan-jie ◽  
...  
Keyword(s):  
Stem Cells ◽  
Molecular Weight ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
High Performance ◽  
The Other ◽  
Proliferation Index ◽  
Blank Group ◽  
Marrow Mesenchymal Stem Cells ◽  
Rat Bone

AbstractThe effects of antler polypeptide on rat bone marrow mesenchymal stem cells (BMSCs) were investigated. Antler polypeptide was separated from Colla Cornus Cervi by ultrafiltration into different samples according to molecular weight: A (molecular weight <800 Da), B (molecular weight 800-1500 Da) and C (molecular weight >1500 Da). The content of antler polypeptide in A, B and C solutions were quantified by high-performance liquid chromatography (HPLC). The effects of antler polypeptide at different concentrations on the proliferation, cell cycle, and osteogenesis of BMSCs were investigated. The highest cell proliferation rate (84.66%) was observed for antler polypeptide B at a concentration of 1.578 × 10−2 g/mL. Antler polypeptide B significantly promoted the proliferation of BMSCs with a proliferation index of 38.68%, which was significantly higher than that of the other groups. Antler polypeptide B significantly enhanced the activity of alkaline phosphatase in BMSCs compared to that of blank group (P <0.001). Antler polypeptide B increased the BMP7 protein expression in BMSCs. Our data suggested that antler polypeptide may promote the proliferation and osteogenic differentiation of BMSCs.

scholarly journals Linker histone H1.2 and H1.4 affect the neutrophil lineage determination

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Gabriel Sollberger ◽  
Robert Streeck ◽  
Falko Apel ◽  
Brian Edward Caffrey ◽  
Arthur I Skoultchi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Critical Role ◽  
Human Cell Line ◽  
Linker Histone ◽  
High Turnover ◽  
Hematopoietic Stem ◽  
Murine Bone Marrow ◽  
A Genome ◽  
And Function

Neutrophils are important innate immune cells that tackle invading pathogens with different effector mechanisms. They acquire this antimicrobial potential during their maturation in the bone marrow, where they differentiate from hematopoietic stem cells in a process called granulopoiesis. Mature neutrophils are terminally differentiated and short-lived with a high turnover rate. Here, we show a critical role for linker histone H1 on the differentiation and function of neutrophils using a genome-wide CRISPR/Cas9 screen in the human cell line PLB-985. We systematically disrupted expression of somatic H1 subtypes to show that individual H1 subtypes affect PLB-985 maturation in opposite ways. Loss of H1.2 and H1.4 induced an eosinophil-like transcriptional program, thereby negatively regulating the differentiation into the neutrophil lineage. Importantly, H1 subtypes also affect neutrophil differentiation and the eosinophil-directed bias of murine bone marrow stem cells, demonstrating an unexpected subtype-specific role for H1 in granulopoiesis.

scholarly journals Functionally Improved Mesenchymal Stem Cells to Better Treat Myocardial Infarction

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Zhi Chen ◽  
Long Chen ◽  
Chunyu Zeng ◽  
Wei Eric Wang
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Clinical Trials ◽  
Causes Of Death ◽  
The Other ◽  
Preclinical Studies ◽  
Significant Progress ◽  
Poor Survival ◽  
And Function ◽  
Host Myocardium

Myocardial infarction (MI) is one of the leading causes of death worldwide. Mesenchymal stem cell (MSC) transplantation is considered a promising approach and has made significant progress in preclinical studies and clinical trials for treating MI. However, hurdles including poor survival, retention, homing, and differentiation capacity largely limit the therapeutic effect of transplanted MSCs. Many strategies such as preconditioning, genetic modification, cotransplantation with bioactive factors, and tissue engineering were developed to improve the survival and function of MSCs. On the other hand, optimizing the hostile transplantation microenvironment of the host myocardium is also of importance. Here, we review the modifications of MSCs as well as the host myocardium to improve the efficacy of MSC-based therapy against MI.

Co-Transplantation of MSC Improves the Engraftment of HSC after Auto-iBMT in Non-Human Primates.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2321-2321
Author(s):  
Shigeo Masuda ◽  
Yoko Obara ◽  
Naohide Ageyama ◽  
Hiroaki Shibata ◽  
Tamako Ikeda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Osteoblastic Differentiation ◽  
The Body ◽  
The Other ◽  
Hematopoietic Stem ◽  
Cynomolgus Monkeys ◽  
Colony Pcr ◽  
Marrow Cavity

Abstract [Background] Mesenchymal stem cells (MSC) have been shown to play critical roles in various in vivo phenomena including osteoblastic differentiation. It has been suggested that, in the bone marrow, hematopoietic stem cells (HSC) reside in osteoblastic niche, which consists of osteoblasts derived from MSC. In mice, previous studies have demonstrated that co-transplantation of MSC improves the engraftment of HSC, especially after transplantation of the cells into the bone marrow cavity directly, namely intra-bone marrow transplantation (iBMT). However, neither the efficacy nor the dynamics such as migration and homing of HSC after iBMT with MSC have been determined in large animals. Here, using non-human primates, we have investigated the effects of co-transplantation of MSC on the engraftment of HSC after autologus iBMT. [Methods] Auto-iBMT of cynomolgus monkeys was performed, using bone marrow stromal cells (as MSC) and CD34-positive cells (as HSC). The latter were divided into two equal aliquots, each of which was genetically marked with a different retroviral vector, G1Na or LNL6. Conditioning of iBMT, TBI or administration of busulfan, was followed by hemi-iBMT; that is, the bone marrow of one side (right or left) of the body was transplanted with one HSC aliquot together with MSC, whereas the other side of the identical body was transplanted with the other HSC aliquot alone. Engraftment of each HSC aliquot was evaluated by colony PCR of bone marrow, as well as by PCR of the genomic DNA obtained from peripheral blood or bone marrow of humerus, femur, and ilium. Both PCR could distinguish the dual markings derived from the two HSC aliquots. [Results] In the first monkey transplanted, we found that the engraftment derived from the co-transplantation aliquot was 4.4-times higher than that derived from the HSC alone aliquot as assessed by colony PCR (48% versus 11%) using the bone marrow samples obtained from the ilium at day 46 post-iBMT. In the second monkey, when the peripheral WBC recovered to 2500–3000/μl after day 28 post-iBMT, 2% of the cells were positive with the retroviral marking derived from the co-transplantation aliquot, although none of them were positive with that derived from the HSC alone aliquot. In addition, colony PCR of the humerus and femur of both sides at day 39 post-iBMT revealed that the engraftment derived from the co-transplantation aliquot was 6.0-times higher than that derived from the HSC alone aliquot. Notably, colony-forming units (CFU) derived from the cotransplantation aliquot were detected in the bone marrow of the opposite side, suggesting that HSC injected into the bone marrow might migrate and achieve homing in the distant bone marrow. [Conclusion] Taken together, these results indicate that, in auto-iBMT of cynomolgus monkeys, co-transplantation of MSC improves the engraftment of HSC, the efficacy of which might be attributable to additional osteoblastic niche, presumably created from co-transplanted MSC.

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