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*
Department of Internal Medicine, Jikei University School of Medicine,
Tokyo, Japan
Department of Microbiology, Jikei University School of Medicine, Tokyo,
Japan
Department of Internal Medicine, Saitama Medical Center, Saitama Medical
School, Saitama, Japan
Research Institute for Microbial Diseases, Osaka University, Osaka,
Japan
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Department of Molecular Pathology, Tokyo Metropolitan Institute of
Gerontology, Tokyo, Japan.
Correspondence to Dr. Toshiyuki Imasawa, Institute of Medical Science and Department of Medicine, Tokai University School of Medicine, Bohseidai Isehara Kanagawa 259-1131, Japan. Phone: 81-463-93-1121 x2713; Fax: 81-463-93-1938; E-mail: imasawa{at}nifty.com
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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B6] mice). After the recipients of donor
BMC manifested GFP-positive cells in their glomeruli, the numbers of such
cells increased markedly, in a time-dependent manner, from 2 wk to 24 wk after
bone marrow transplantation. Immunohistochemical analyses revealed that most
GFP-positive cells in the glomeruli were neither macrophages nor T cells. With
the use of a laser-scanning confocal microscope, GFP-positive cells were
observed within the mesangium of [GFPB6] mice. Furthermore, indirect
immunofluorescence assays demonstrated that desmin-positive cells in the
glomeruli of these chimeric mice were also positive for GFP. Among glomerular
cells isolated from [GFPB6] mice 24 wk after bone marrow transplantation
and then cultured, the majority of cells (approximately 84%) stained for
desmin and approximately 60% of the desmin-positive cells expressed GFP. In
addition, these GFP-positive cells in the cultures contracted in response to
angiotensin II stimulation. These results suggest that bone marrow-derived
cells may have the potential to differentiate into glomerular mesangial
cells. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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BMC clearly have the potential to differentiate into not only hematopoietic lineages but also mesenchymal lines (5). Both in vivo and in vitro, BMC have served as precursor cells for bone, cartilage, lung parenchyma, muscle, and hepatic cells in irradiated or immunodeficient animals (6,7,8,9,10,11). In addition, stem cells have been identified in adult tissues undergoing extensive cell replacement because of physiologic turnover or injury (12).
During embryonic glomerulogenesis, cells of the metanephric mesenchyme apparently have the capacity to convert into glomerular epithelial cells, whereas endothelial cells are derived from precursor endothelial cells, rather than the metanephric mesenchyme (13,14,15). In the anti-Thy-1 model of mesangial proliferative glomerulonephritis, repopulation of the mesangium after injury results from the migration of mesangial cell-like cells that reside in the juxtaglomerular apparatus (16,17). However, whether the mesangial cells routinely originate from the metanephric mesenchyme or from the endothelial cell lineage is still debatable.
We hypothesized that glomerular cells in nephritic mice that have been cleansed of their destructive cells and then treated with BMT might be repopulated by donor cells, with prevention of the otherwise obligatory glomerular lesions. To clarify this issue, we transplanted BMC from mice transgenic for green fluorescence protein (GFP) into syngeneic C57BL/6j (B6) mice. Because all tissues from GFP-transgenic mice (green mice), with the exception of erythrocytes and hair, are green under excitation light (18), GFP-positive donor cells in the recipients are readily identifiable. Our findings demonstrated that BMC might have the potential to differentiate into glomerular cells.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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BMT
In preliminary experiments, a single 8.0-Gy dose of total-body irradiation
from a 60Co source killed all 8-wk-old female B6 mice by 3 wk after
the irradiation if subsequent BMT was not performed. In spleens of these
irradiated mice, no hematopoietic colonies were macroscopically visible 14 d
after irradiation, indicating that no pluripotential stem cells were present
(19). On the basis of these
results, we irradiated recipient female B6 mice, at 8 wk of age, with 8.0 Gy.
BMC obtained from pelvic, femoral, and peroneal bones of donors were incubated
with anti-Thy-1.2 antibody (Ab) (F7D5; Serotec Ltd., Oxford, England), at an
appropriate concentration, on ice for 30 min and were then reacted with
complement (Cedar Lane, Ontario, Canada) at 37°C for 30 min, as described
previously (3). Five to 6 h
after irradiation, the recipient B6 mice received injections, through the tail
vein, of 1 x 107 T cell-depleted BMC from 8-wk-old GFP mice
([GFPB6]) or from 8-wk-old B6 mice ([B6B6]).
Cytofluorometric Analyses
Spleen cells were gently homogenized and depleted of red blood cells in
Tris-buffered ammonium chloride (pH 7.2). Pelvic, femoral, and peroneal bone
BMC were washed three times with phosphate-buffered saline (PBS), after which
1 x 106 splenic cells and BMC were resuspended in 1%
paraformaldehyde (PFA)-PBS and analyzed with a flow cytometer (EPICS CS;
Coulter Electronics, Hialeah, FL). Cells expressing GFP were detectable at the
same wavelength as used for FITC detection (488 nm).
Morphometric Analyses
At 2 (n = 3), 4 (n = 3), 8 (n = 3), and 24
(n = 5) wk after BMT, we performed histologic analyses of the kidneys
from [GFPB6] mice, which had been sufficiently perfused with 25 ml of
PBS and 25 ml of 3% formalin-PBS for removal of circulating cells from the
glomeruli. For light microscopy, tissue samples were then fixed with 3%
formalin-PBS and embedded in paraffin. After sectioning, the tissues were
stained with periodic acid-Schiff reagent. The numbers of cells in the
glomeruli were counted individually for >20 glomeruli/cross-section, and a
mean value was determined for each section. GFP-positive cells in the
glomeruli were observed with a laser-scanning confocal microscope (LSM)
(LSM410; Zeiss, Oberkochen, Germany) at 2, 4, 8, and 24 wk after BMT.
Formalin-fixed sections (0.5 mm) were mounted in 10% gelatin-PBS. The numbers
of GFP-positive cells in the glomeruli were counted for >20 glomeruli, and
a mean value was determined for each section.
For clear identification of the locations of GFP-positive cells within glomeruli, mice at the 24th week after BMT (n = 3) were perfused with 25 ml of PBS and 25 ml of 2% PFA-PBS. Tissue samples were fixed with 2% PFA-PBS for 2 h at 4°C and then washed with 6.8% sucrose-PBS overnight at 4°C. Tissues were then embedded in Tecknovit 8100 (cold polymerizing resin; Heraeus Kulzer, Wehrheim, Germany), according to the instructions provided by the manufacturer. Finally, the sections (2 µm) were observed with the LSM, and digitized images were obtained by using LSM software version 3.5 (based on Windows version 3.1).
Immunohistochemical Analyses
Tissue samples from the chimeric mice at the 24th week after BMT
(n = 3) were fixed with 2% PFA-PBS, washed with 6.8% sucrose-PBS
(same samples used in the Tecknovit 8100 analysis described above), embedded
in OCT compound (Miles Scientific, Naperville, IL), and quickly frozen in dry
ice-acetone. Cryostat sections (4 µm) were fixed in cold acetone for 10
min. After being washed with PBS, the sections were incubated with polyclonal
rabbit anti-desmin Ab (ICN Pharmaceuticals, Cleveland, OH) at 4°C
overnight, followed by rinsing in PBS and incubation at 37°C for 60 min
with rhodamine-conjugated sheep anti-rabbit IgG Ab (ICN Pharmaceuticals). The
sections were rinsed again in PBS, mounted with SlowFade antifade kits
(Molecular Probes, Eugene, OR), and observed with the LSM. The detection of
infiltrating F4/80-positive macrophages or Thy-1-positive T cells relied on
immunohistochemical analyses based on the avidin-biotin-peroxidase method.
First, the endogenous biotins in the sections were blocked, as directed, with
an avidin-biotin blocking kit (Vector Laboratories, Burlingame, CA). Next, the
sections were incubated with primary Ab overnight at 4°C. Primary Ab were
used in this study as follows: rat anti-mouse F4/80 monoclonal Ab (mAb) (BMA
Biomedicals AG, Augst, Switzerland) for macrophage staining and rat anti-mouse
Thy-1.2 mAb (30-H12; Pharmingen, San Diego, CA) for T cell staining. The
sections were then incubated with biotinylated mouse anti-rat IgG (
chain) mAb (MARK-1; Zymed Laboratories, San Francisco, CA) for 60 min at room
temperature and were further incubated with avidin-biotin-peroxidase complex
(Vector ABC Elite staining kit; Vector Laboratories). The peroxidase was
developed with a diaminobenzidine substrate solution (peroxidase substrate
kit; Vector Laboratories). Both kits were used according to the instructions
provided by the manufacturer. Finally, the sections were counterstained with
methyl green. For the staining of macrophage scavenger receptors and MHC class
II molecules, we used rat anti-mouse macrophage scavenger receptor mAb (clone
2f8; Serotec) and rat anti-mouse MHC class II mAb (clone ER-TR3; BMA
Biomedicals), respectively, as primary Ab. Texas red-labeled mouse anti-rat
IgG Ab was used as the second Ab (Jackson ImmunoResearch, West Grove, PA).
Four-micrometer sections were fixed in acetone for 10 min at 4°C and
rinsed in PBS. Primary Ab were allowed to bind during a 1-h incubation at
37°C. Sections were then washed in PBS and incubated with the second Ab
for 1 h at 37°C. Negative control experiments were performed by replacing
the firststep Ab with incubation buffer only or with isotype-matched Ab. We
counted the number of GFP-positive/scavenger receptor-positive cells and
GFP-positive/MHC class II-positive cells in the glomeruli of the chimeric mice
at the 24th week after BMT.
Culture of Glomerular Cells
Kidneys were obtained from [GFPB6] mice 24 wk after BMT (n =
3). The glomeruli were isolated by differential sieving, as reported
previously (20), and were then
plated on chamber slides coated with collagen I (BIOCOAT culture slides;
Falcon, Becton Dickinson Labware, Mountain View, CA). In our experiments, the
purity of the glomerulus preparation was >90% and few tubular cells were
contaminating the cultures, as determined by microscopy. The culture medium
was Dulbecco's modified Eagle's medium (DMEM)/F12 (1:1) (Life Technologies,
Grand Island, NY) supplemented with 20% fetal bovine serum (FBS) (REHATUIN;
Intergen, Purchase, NY). The cells were maintained in a humidified atmosphere
with 5% CO2 at 37°C. Within 2 wk, most primary cultures
exhibited an irregular stellate shape. The identity of the cultured cells was
confirmed by immunofluorescence detection with specific Ab and assessment of
responses against angiotensin II (AngII) (see below).
Cell Culture Immunofluorescence Assays
Cells grown on chamber slides were fixed with 2% PFA-PBS for 10 min at room
temperature. After being washed with PBS, cells were permeabilized with 0.1%
Triton X-100 (Sigma Chemical Co., St. Louis, MO) in PBS for 1 min at room
temperature and were washed again. Nonspecific binding of avidin and biotin
was prevented by using an ABC blocking kit, as recommended by the manufacturer
(Vector Laboratories). After being washed with PBS, the cells were incubated
for 2 h at 37°C with one of the following Ab: rabbit antiserum against
desmin (ICN Pharmaceuticals), rabbit antiserum against factor VIII-related
antigen (Zymed), or mouse IgG mAb against cytokeratin (Zymed). The cells were
rinsed in PBS and incubated with biotin-labeled sheep anti-rabbit IgG Ab
(American Qualex, La Mirada, CA) or biotin-labeled rabbit anti-mouse IgG Ab
(American Qualex) for 1 h at 37°C, followed by incubation with
rhodaminelabeled avidin (Molecular Probes, Eugene, OR) for 1 h at 37°C.
The cells were again rinsed in PBS, mounted using SlowFade antifade kits, and
observed with a LSM. Negative control experiments were performed by replacing
the first-step Ab with incubation buffer only or with isotype-matched Ab.
AngII Stimulation of Cells in Culture
Cells grown on chamber slides were washed with serum-free DMEM and left on
slides for 10 min at room temperature. The cells were then exposed to
10-6 M AngII (Sigma Chemical Co., St. Louis, MO) at room
temperature, as reported previously
(20). Before and after
stimulation with AngII for 10 min, photographs of the same field were taken
under high magnification (x2400). In control experiments, cells were
exposed to the vehicle without AngII; photographs were taken before and after
exposure to the vehicle for 10 min.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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B6] chimeric mice were negative for GFP, the cells
from GFP-transgenic mice were GFP-positive (86.9 ± 6.2% in splenic
lymphocytes and 64.3 ± 6.0% in BMC). Two weeks after BMT, 85.2 ±
5.0% of splenic lymphocytes and 64.3 ± 3.6% of BMC from [GFPB6]
chimeric mice were positive for GFP. The percentages of GFP-positive spleen
cells and BMC of [GFPB6] mice were comparable to those of GFP mice and
remained consistently so until 24 wk after BMT, indicating that the recipient
B6 mice had been completely reconstituted with BMC of GFP mouse origin.
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The Number of GFP-Positive Cells in the Glomeruli from [GFPB6]
Mice Increased in a Time-Dependent Manner after BMT
After sufficient perfusion of chimeric mice with PBS to remove circulating
GFP-positive cells from their glomeruli, the histologic appearance of the
kidneys was assessed at 2, 4, 8, and 24 wk after BMT. As assessed by light
microscopy, there was neither mesangial hypercellularity of the glomeruli nor
tubulointerstitial injury in [GFPB6] mice
(Figure 1, A and B). Similarly,
in the quantitative analysis, the number of glomerular cells in these mice did
not change throughout the observation period
(Figure 2). As assessed with a
LSM, few GFP-positive cells were observed in [GFPB6] mice 2 wk after BMT
(Figure 1C). However,
GFP-positive cells were clearly visible in the glomeruli, the periglomerular
space, and the interstitium of [GFPB6] mice 4 wk after BMT, and these
green cells were consistently observed in the kidneys of the recipients until
24 wk after BMT (Figure 1D).
Moreover, the number of glomerular GFP-positive cells in [GFPB6] mice
increased in a time-dependent manner (2 wk, 0.67 ± 0.67/glomerular
cross-section; 4 wk, 4.18 ± 0.22/glomerular cross-section; 8 wk, 8.20
± 2.15/glomerular cross-section; 24 wk, 12.78 ± 1.68/glomerular
cross-section; means ± SEM) (Figure
2). However, [B6B6] mice (n = 3 at each observation
point) exhibited no GFP-positive cells in glomeruli at any observation
time.
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GFP-Positive Cells in the Glomeruli of [GFPB6] Mice Were
Neither Infiltrating Macrophages nor T Cells
To investigate whether the GFP-positive cells in glomeruli were adherent
macrophages or T cells, we performed F4/80 staining for macrophages
(monocytes) and Thy-1 staining for pan-T cells. F4/80-positive cells and
Thy-1-positive cells were barely observed in glomeruli of [GFPB6] mice
at 24 wk after BMT (means ± SEM of 0.19 ± 0.09/glomerular
cross-section and 0.49 ± 0.05/glomerular cross-section, respectively)
(Figure 3, A and B). Furthermore, the expression of macrophage scavenger receptors and MHC class II
molecules was examined. Only 5% of glomerular GFP-positive cells were positive
for macrophage scavenger receptors (Figure
3, C1 and C2), and only 6% of glomerular
GFP-positive cells were positive for MHC class II molecules (data not shown).
These data suggest that most GFP-positive cells in the glomeruli might be
neither macrophages nor T cells.
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Reconstitution of the Mesangium with BMC of Donor Origin Occurred in
[GFPB6] Mice
To clarify the localization of GFP-positive cells in the glomeruli, we next
examined the differential interference contrast images of glomeruli with
fluorescence imaging. As shown in Figure
4, some GFP-positive cells were located within the mesangium 24 wk
after BMT. To identify the character of these cells, we examined the
expression of desmin, which is a marker for mesangial cells, using indirect
immunofluorescence with a specific Ab (anti-desmin). As shown in
Figure 5, some of the
desmin-positive cells were also positive for GFP in the nuclei, suggesting
that the mesangial cells of the recipients consisted of donor BMC.
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Cultured GFP-Positive Cells Isolated from the Glomeruli of
[GFPB6] Mice Were Positive for Desmin Staining and Exhibited Contractile
Properties in Response to AngII Stimulation
To confirm that GFP-positive cells within the mesangium in [GFPB6]
mice exhibited the characteristics of mesangial cells, we isolated glomeruli
from these chimeric mice at 24 wk after BMT and cultured them in DMEM/F12 with
20% FBS. Two weeks later, GFP-positive cells, which exhibited stellate
morphologic features, were clearly observed to be migrating from the glomeruli
(Figure 6A). In
immunofluorescence assays, the majority of cultured cells (approximately 84%)
stained for desmin and approximately 60% of desmin-positive cells expressed
GFP in their nuclei (Figure 6, B through
D). These cultured cells did not exhibit staining when anti-desmin
Ab was replaced by incubation buffer or by isotype-matched Ab. In addition,
most of the cultured cells were negative for cytokeratin and factor
VII-related antigen staining (data not shown). Therefore, these GFP-positive
cells cultured from glomeruli of [GFPB6] mice exhibited several
characteristic features of mesangial cells
(20,21).
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To further investigate whether the cultured GFP-positive cells exhibited
functional properties similar to those of contractile mesangial cells, we
examined the morphologic changes of these cells after AngII exposure
(20). The GFP-positive cells
from isolated glomeruli of [GFPB6] mice did not exhibit any morphologic
changes when exposed to the vehicle without AngII for 10 min
(Figure 7, A and B). In
contrast, compared with findings before AngII exposure
(Figure 7C), the GFP-positive
cells exhibited structural alterations, i.e., sharpening or
disappearance of the cytoplasmic processes or withdrawal of the forefront of
the cytoplasm (Figure 7D). Therefore, the GFP-positive cells exhibited properties functionally similar to
those of mesangial cells in response to AngII stimulation.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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B6] mice were comparable to those of GFP mice
(Table 1), suggesting that the
B6 recipients had been almost completely reconstituted with BMC of GFP mouse
origin. Light microscopic findings revealed that the glomeruli in
[GFPB6] mice demonstrated no leukocyte infiltration and no mesangial
hypercellularity (Figures 1, A and
B, and 3).
Throughout the observation period, no albuminuria was detected in any animals
with the single radial immunodiffusion method (data not shown). These
observations indicated that BMT with 8.0-Gy, total-body irradiation did not
induce remarkable changes in renal function and structure.
Of note, at 4 wk after BMT, GFP-positive cells were clearly observed in the
glomeruli, the periglomerular space, and the interstitium in [GFPB6]
mice. Two weeks after BMT, peripheral lymphocytes were almost completely
replaced by donor-derived cells. Therefore, if circulating cells had remained
in glomeruli after perfusion with our method, GFP-positive cells should have
been observed in glomeruli 2 wk after BMT. In fact, very few GFP-positive
cells were present in glomeruli 2 wk after BMT
(Figure 1C). Therefore, we
speculated that the kidney perfusion should be sufficient to remove
circulating and nonadherent cells from glomeruli, and most GFP-positive cells
in glomeruli from 4 wk after BMT were other cell types. Furthermore, the
number of glomerular GFP-positive cells in these chimeric mice increased with
time (Figure 2) but was
independent of the GFP-positive cellular content of the splenic lymphocytes
and bone marrow (Table 1).
Twenty-four weeks after BMT, the mean number of GFP-positive cells/glomerular
section was 12.78 ± 1.68. One year after BMT, many more GFP-positive
cells were observed in the glomeruli of [GFPB6] mice (data not shown).
Previously, bone marrow-derived, Ia-positive cells were also noted in the
mesangium (22). For this
study, we sufficiently perfused the chimeric mice with PBS to remove
circulating GFP-positive cells from their glomeruli. The number of glomerular
cells in these mice did not change throughout the observation period (Figures
1 and
2). Immunohistologic studies
revealed that few F4/80-positive or Thy-1-positive cells were observed in the
glomeruli of [GFPB6] mice 24 wk after BMT
(Figure 3, A and B). In
addition, most GFP-positive cells (Figure
3C1) in the glomeruli of [GFPB6] mice did not
express macrophage scavenger receptors
(Figure 3C2) or MHC
class II molecules (data not shown). These results suggest that the
GFP-positive cells in the glomeruli of these chimeric mice were neither
adherent macrophages nor T cells; rather, donor green BMC replenished resident
glomerular cells.
The LSM revealed that some GFP-positive green cells resided within the
mesangium of glomeruli from [GFPB6] mice
(Figure 4). To characterize
these cells, we used indirect immunofluorescence assays and an Ab against
desmin, a well known marker for mesangial cells
(20,21).
With this method, a portion of the desmin-positive mesangial cells were also
positive for GFP, as shown in Figure
5. These data indicate that mesangial cells in the B6 recipients
had been replenished by GFP donor BMC.
To confirm that GFP-positive cells in the glomeruli exhibited the
characteristics of mesangial cells, we isolated glomeruli from [GFPB6]
mice at 24 wk after BMT and cultured them in DMEM/F12 with 20% FBS.
Subsequently, most of these cultured cells stained for desmin, and
approximately 60% of the desmin-positive cells expressed GFP
(Figure 6). The presumed source
of these desmin-positive/GFP-positive cells was the donor BMC, whereas the
desmin-positive/GFP-negative cells may have originated from the B6 recipients.
In addition, most of the cultured cells were negative for both cytokeratin, a
marker for glomerular epithelial cells, and factor VIII-related antigens,
which typify glomerular endothelial cells
(20). Finally, after exposure
to AngII stimulation, these GFP-positive cells demonstrated the contractile
properties of mesangial cells (Figure
7). These characteristic features suggest that the GFP-positive
cells from the glomeruli of [GFPB6] mice are mesangial cells. It was
recently reported that the hematopoietic transcription factor PU.1 protein was
identified within nuclear extracts of mesangial cells
(23). That study supports our
observations that glomerular mesangial cells may be derived from BMC.
How we can explain the restoration of mesangial cells in the BMT-treated mice by donor BMC? Several recent studies demonstrated that BMC serve as precursor cells for various mesenchymal tissues (5,6,7,8,9,10,11). Takahashi et al. (24) previously reported that the proportion of endothelial progenitor cells in the circulation was approximately 10% in normal B6 mice. We then considered that a mesangial progenitor cell-enriched population might exist in the circulation, and we hypothesized that these precursors might journey into the mesangial area and differentiate into mesangial cells as a normal event or after injury. The renewal rate of mesangial cells has been estimated to be approximately 1%/d (25). Because in this study recipient mice were irradiated, we could not exclude the effect of radiation on mesangial cells and their turnover rates. Another possibility is that bone marrow-derived mesangial precursor cells may reside in the extraglomerular mesangium. Recently, Hugo et al. (16) indicated that the juxtaglomerular apparatus has a role in maintaining the size of the mesangial cell population after injury in the anti-Thy-1 model of mesangial proliferative glomerulonephritis. Therefore, in this study, bone marrow-derived mesangial progenitor cells might reside in the juxtaglomerular apparatus and migrate into the mesangium. Additional studies are needed to investigate the origin of mesangial progenitor cells.
GFP-positive cells were also found in the heart, liver, and vessels in our
[GFPB6] mice. Recent studies demonstrated that platelet-derived growth
factor and vascular endothelial growth factor and their receptors are
essential molecules for glomerulogenesis
(17,26,27).
In addition, mice deficient in laminin 
3 exhibit abnormalities in the
development of glomerular endothelial and mesangial cells
(28). Although we still have
no data on the mechanisms underlying the differentiation of BMC into mesangial
cells, it is thought that some growth factors and extracellular matrix
components locally produced by resident glomerular cells in BMT recipients
might play an important role in the supplementation by donor BMC.
Furthermore, the data presented here may support the notion that BMT from normal donors can attenuate glomerular injury by replacing harmful immune cells and replenishing glomerular cells in nephritic recipients (3). Therefore, BMT may offer new insights into the mechanisms that promote glomerular diseases and may also provide a new approach for the treatment of these diseases.
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Acknowledgments |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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J.-K. Guo, A. Schedl, and D. S. Krause Bone Marrow Transplantation Can Attenuate the Progression of Mesangial Sclerosis Stem Cells, February 1, 2006; 24(2): 406 - 415. [Abstract] [Full Text] [PDF]
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J. Perry, S. Tam, K. Zheng, Y. Sado, H. Dobson, B. Jefferson, R. Jacobs, and P. S. Thorner Type IV Collagen Induces Podocytic Features in Bone Marrow Stromal Stem Cells In Vitro J. Am. Soc. Nephrol., January 1, 2006; 17(1): 66 - 76. [Abstract] [Full Text] [PDF]
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T. Yokota, Y. Kawakami, Y. Nagai, J.-x. Ma, J.-Y. Tsai, P. W. Kincade, and S. Sato Bone Marrow Lacks a Transplantable Progenitor for Smooth Muscle Type {alpha}-Actin-Expressing Cells Stem Cells, January 1, 2006; 24(1): 13 - 22. [Abstract] [Full Text] [PDF]
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T.-C. Fang, M. R. Alison, H. T. Cook, R. Jeffery, N. A. Wright, and R. Poulsom Proliferation of Bone Marrow-Derived Cells Contributes to Regeneration after Folic Acid-Induced Acute Tubular Injury J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1723 - 1732. [Abstract] [Full Text] [PDF]
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C. Bos, Y. Delmas, A. Desmouliere, A. Solanilla, O. Hauger, C. Grosset, I. Dubus, Z. Ivanovic, J. Rosenbaum, P. Charbord, et al. In Vivo MR Imaging of Intravascularly Injected Magnetically Labeled Mesenchymal Stem Cells in Rat Kidney and Liver Radiology, December 1, 2004; 233(3): 781 - 789. [Abstract] [Full Text] [PDF]
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 F. Zheng, F. Cornacchia, I. Schulman, A. Banerjee, Q.-l. Cheng, M. Potier, A. R. Plati, M. Berho, S. J. Elliot, J. Li, et al. Development of Albuminuria and Glomerular Lesions in Normoglycemic B6 Recipients of db/db Mice Bone Marrow: The Role of Mesangial Cell Progenitors Diabetes, September 1, 2004; 53(9): 2420 - 2427. [Abstract] [Full Text] [PDF]
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O. Y. Jones, A. Steele, J. M. Jones, Y. Marikar, Y. Chang, A. Feliz, R. A. Cahill, and R. A. Good Nonmyeloablative Bone Marrow Transplantation of BXSB Lupus Mice Using Fully Matched Allogeneic Donor Cells from Green Fluorescent Protein Transgenic Mice J. Immunol., May 1, 2004; 172(9): 5415 - 5419. [Abstract] [Full Text] [PDF]
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M. El Nahas Kidney remodelling and scarring: the plasticity of cells Nephrol. Dial. Transplant., October 1, 2003; 18(10): 1959 - 1962. [Full Text] [PDF]
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 M. B. Rookmaaker, A. M. Smits, H. Tolboom, K. van 't Wout, A. C. Martens, R. Goldschmeding, J. A. Joles, A. J. van Zonneveld, H.-J. Grone, T. J. Rabelink, et al. Bone-Marrow-Derived Cells Contribute to Glomerular Endothelial Repair in Experimental Glomerulonephritis Am. J. Pathol., August 1, 2003; 163(2): 553 - 562. [Abstract] [Full Text] [PDF]
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J. R. Timoshanko, J. D. Sedgwick, S. R. Holdsworth, and P. G. Tipping Intrinsic Renal Cells Are the Major Source of Tumor Necrosis Factor Contributing to Renal Injury in Murine Crescentic Glomerulonephritis J. Am. Soc. Nephrol., July 1, 2003; 14(7): 1785 - 1793. [Abstract] [Full Text] [PDF]
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 R. Passier and C. Mummery Origin and use of embryonic and adult stem cells in differentiation and tissue repair Cardiovasc Res, May 1, 2003; 58(2): 324 - 335. [Abstract] [Full Text] [PDF]
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