Engineering Renal

8/10/2019 Engineering Renal

1/7

Contents

60.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 869

60.2 Basic Components . . . . . . . . . . . . . . . . . . . . 869

60.3 Approaches for Renal Tissue Regeneration 870

60.3.1 Developmental Approaches . . . . . . . . . . . . . 870

60.3.2 Tissue Engineering Approaches . . . . . . . . . 871

60.4 Regeneration of Functional Tissue In Vivo 872

60.5 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . 874

References . . . . . . . . . . . . . . . . . . . . . . . . . . 874

individuals. Although dialysis can prolong survival

via ltration, other kidney functions are not replaced,

leading to long-term consequences such as anemiaand malnutrition [2, 3, 7]. Currently, renal transplan-

tation is the only denitive treatment that can restore

full kidney function. However, transplantation has

several limitations, such as critical donor shortage,

complications due to chronic immunosuppressive

therapy and graft failure [2, 3, 7].

The limitations of current therapies for renal

failure have led investigators to explore the devel-

opment of alternative therapeutic modalities that

could improve, restore, or replace renal function.

The emergence of cell-based therapies using tissueengineering and regenerative medicine strategies has

presented alternative possibilities for the manage-

ment of pathologic renal conditions [1, 713]. The

concept of kidney cell expansion followed by cell

transplantation using tissue engineering and regen-

erative medicine techniques has been proposed as a

method to augment either isolated or total renal func-

tion. Despite the fact that the kidney is considered to

be one of the more challenging organs to regenerate

and/or reconstruct, investigative advances made to

date have been promising [8, 1012].

60.2

Basic Components

The unique structural and cellular heterogeneity

present within the kidney creates many challenges

for tissue regeneration. The system of nephrons and

60.1

Introduction

The kidney is a vital and complex organ that per-

forms many critical functions [13]. It is responsible

for ltering the bodys wastes, such as urea, from the

blood and excreting them as urine. In addition to the

excretory function, the kidney maintains the bodys

homeostasis by regulating acid-base balance, bloodpressure, and plasma volume. Moreover, it synthe-

sizes 1, 25 vitamin D3, erythropoietin, glutathione,

and free radical scavenging enzymes. It is also known

that the kidney participates in the catabolism of low

molecular weight proteins and in the production and

regulation of cytokines [46].

There are many conditions where the kidney

functions are diminished and these lead to renal

failure. End stage renal failure is a devastating con-

dition which involves multiple organs in affected

Regeneration of Renal Tissues

T. Aboushwareb, J. J. Yoo, A. Atala


2/7

collecting ducts within the kidney is composed of

multiple functionally and morphologically distinct

segments. For this reason, appropriate conditions

need to be provided for the long-term survival, dif-

ferentiation, and growth of many types of cells. Re-

cent efforts in the area of kidney tissue regeneration

have focused on the development of a reliable cellsource [1419]. In addition, optimal growth condi-

tions have been extensively investigated to provide

an adequate enrichment to achieve stable renal cell

expansion systems [2024].

Isolation of particular cell types that produce spe-

cic factors, such as erythropoietin, may be a good

approach for selective cell therapies. However, to-

tal renal function would not be achieved using this

approach. To create kidney tissue that would deliver

full renal function, a culture containing all of the cell

types comprising the functional nephron units shouldbe used. Optimal culture conditions to nurture renal

cells have been extensively studied and the cells

grown under these conditions have been reported

to maintain their cellular characteristics [25]. Fur-

thermore, renal cells placed in a three-dimensional

culture environment are able to reconstitute renal

structures.

Recent investigative efforts in the search for a re-

liable cell source have been expanded to stem and

progenitor cells. The use of these cells for tissue re-

generation is attractive due to their ability to differen-tiate and mature into specic cell types required for

regeneration. This is particularly useful in instances

where primary renal cells are unavailable due to ex-

tensive tissue damage. Bone marrow-derived human

mesenchymal stem cells have been shown to be a po-

tential source because they can differentiate into sev-

eral cell lineages [14, 15, 18]. These cells have been

shown to participate in kidney development when

they are placed in a rat embryonic niche that allows

for continued exposure to a repertoire of nephrogenic

signals [19]. These cells, however, were found tocontribute mainly to regeneration of damaged glom-

erular endothelial cells after injury. In addition, the

major cell source of kidney regeneration was found

to originate from intrarenal cells in an ischemic renal

injury model [14, 17]. Another potential cell source

for kidney regeneration is circulating stem cells,

which have been shown to transform into tubular and

glomerular epithelial cells, podocytes, mesangial

cells, and interstitial cells after renal injury [15, 16,

2630]. These observations suggest that controlling

stem and progenitor cell differentiation may lead to

successful regeneration of kidney tissues.

Although isolated renal cells are able to retain

their phenotypic and functional characteristics in

culture, transplantation of these cells in vivo may not

result in structural remodeling that is appropriate forkidney tissue. In addition, cell or tissue components

cannot be implanted in large volumes as diffusion

of oxygen and nutrients is limited [31]. Thus, a cell-

support matrix, preferably one that encourages an-

giogenesis, is necessary to allow diffusion across the

entire implant. A variety of synthetic and naturally

derived materials have been examined in order to de-

termine the ideal support structures for regeneration

[9, 3235]. Biodegradable synthetic materials, such

as poly-lactic and poly-glycolic acid polymers, have

been used to provide structural support for cells.Synthetic materials can be easily fabricated and con-

gured in a controlled manner, which make them at-

tractive options for tissue engineering. However, nat-

urally derived materials, such as collagen, laminin,

and bronectin, are much more biocompatible and

provide a similar extracellular matrix environment to

normal tissue. For this reason, collagen-based scaf-

folds have been used in many applications [3639].

60.3

Approaches for Renal

Tissue Regeneration

60.3.1

Developmental Approaches

Transplantation of a kidney precursor, such as the

metanephros, into a diseased kidney has been pro-posed as a possible method for achieving functional

restoration. In an animal study, human embryonic

metanephroi, transplanted into the kidneys of an im-

mune decient mouse model, developed into mature

kidneys [40]. The transplanted metanephroi pro-

duced urine-like uid but failed to develop ureters.

This study suggests that development of an in vitro

system in which metanephroi could be grown may

lead to transplant techniques that could produce a

870 T. Aboushwareb, J. J. Yoo, A. Atala


3/7

small replacement kidney within the host. In another

study, the metanephros was divided into mesenchy-

mal tissue and ureteral buds, and each of the tissue

segments was cultured in vitro [41]. After 8 days in

culture, each portion of the mesenchymal tissues had

grown to the original size. A similar method was

used for ureteral buds, which also propagated. Theseresults indicate that if the mesenchyme and ureteral

buds were placed together and cultured in vitro, a

metanephros-like structure would develop. This sug-

gests that the metanephros could be propagated un-

der optimal conditions.

In another study, transplantation of metanephroi

into a nonimmunosuppressed rat omentum showed

that the implanted metanephroi are able to undergo

differentiation and growth that is not conned by a

tight organ capsule [42]. When the metanephroi with

an intact ureteric bud were implanted, the metanephroiwere able to enlarge and become kidney-shaped tis-

sue within 3 weeks. The metanephroi transplanted

into the omentum were able to develop into kidney

tissue structures with a well-dened cortex and me-

dulla. Mature nephrons and collecting system struc-

tures are shown to be indistinguishable from those of

normal kidneys by light or electron microscopy [43].

Moreover, these structures become vascularized via

arteries that originate at the superior mesenteric ar-

tery of the host [43]. It has been demonstrated that

the metanephroi transplanted into the omentum sur-vive for up to 32 weeks post implantation [44]. These

studies show that the developmental approach may

be a viable option for regenerating renal tissue for

functional restoration.

60.3.2

Tissue Engineering Approaches

The ability to grow and expand cells is one of the

essential requirements in engineering tissues. The

feasibility of achieving renal cell growth, expansion,

and in vivo reconstitution using tissue engineering

techniques was investigated [9]. Donor rabbit kid-

neys were removed and perfused with a nonoxide

solution which promoted iron particle entrapment in

the glomeruli. Homogenization of the renal cortex

and fractionation in 83 and 210 micron sieves with

subsequent magnetic extraction yielded three sepa-

rate puried suspensions of distal tubules, glomeruli,

and proximal tubules. The cells were plated sepa-

rately in vitro and after expansion, were seeded onto

biodegradable polyglycolic acid scaffolds and im-

planted subcutaneously into host athymic mice. This

included implants of proximal tubular cells, glomer-uli, distal tubular cells, and a mixture of all three cell

types. Animals were sacriced at 1 week, 2 weeks,

and 1 month after implantation and the retrieved im-

plants were analyzed. An acute inammatory phase

and a chronic foreign body reaction were seen, ac-

companied by vascular ingrowth by 7 days after im-

plantation. Histologic examination demonstrated pro-

gressive formation and organization of the nephron

segments within the polymer bers with time. Renal

cell proliferation in the cell-polymer scaffolds was

detected by in vivo labeling of replicating cells withthe thymidine analog bromodeoxyuridine [17]. BrdU

incorporation into renal cell DNA was conrmed us-

ing monoclonal anti-BrdU antibodies. These results

demonstrated that renal specic cells can be success-

fully harvested and cultured, and can subsequently

attach to articial biodegradable polymers. The renal

cell-polymer scaffolds can be implanted into host

animals where the cells replicate and organize into

nephron segments, as the polymer, which serves as a

cell delivery vehicle, undergoes biodegradation.

Initial experiments showed that implanted cell-polymer scaffolds gave rise to renal tubular struc-

tures. However, it was unclear whether the tubular

structures reconstituted de novo from dispersed

renal elements, or if they merely represented frag-

ments of donor tubules which survived the original

dissociation and culture processes intact. Further in-

vestigation was conducted in order to examine the

process [45]. Mouse renal cells were harvested and

expanded in culture. Subsequently, single isolated

cells were seeded on biodegradable polymers and

implanted into immune competent syngeneic hosts.Renal epithelial cells were observed to reconstitute

into tubular structures in vivo. Sequential analyses

of the retrieved implants over time demonstrated that

renal epithelial cells rst organized into a cord-like

structure with a solid center. Subsequent canalization

into a hollow tube could be seen by 2 weeks. His-

tologic examination with nephron-segment-specic

lactins showed successful reconstitution of proxi-

mal tubules, distal tubules, loop of Henle, collecting

Chapter 60 Regeneration of Renal Tissues 871


4/7

tubules, and collecting ducts. These results showed

that single suspended cells are capable of reconsti-

tuting into tubular structures, with homogeneous cell

types within each tubule.

60.4

Regeneration of Functional

Tissue In Vivo

The kidneys are critical to body homeostasis because

of their excretory, regulatory, and endocrine func-

tions. The excretory function is initiated by ltration

of blood at the glomerulus, and the regulatory func-

tion is provided by the tubular segments. Although

our prior studies demonstrated that renal cells seededon biodegradable polymer scaffolds are able to

form some renal structures in vivo, complete renal

function could not be achieved in these studies. In

a subsequent study we sought to create a functional

articial renal unit which could produce urine [46].

Mouse renal cells were harvested, expanded in cul-

ture, and seeded onto a tubular device constructed

from polycarbonate [39]. The tubular device was

connected at one end to a silastic catheter which ter-

minated into a reservoir. The device was implanted

subcutaneously in athymic mice. The implanteddevices were retrieved and examined histologically

and immunocytochemically at 1, 2, 3, 4 and 8 weeks

after implantation. Fluid was collected from inside

the implant, and uric acid and creatinine levels were

determined.

Histological examination of the implanted de-

vice demonstrated extensive vascularization as well

as formation of glomeruli and highly organized

tubule-like structures. Immunocytochemical stain-

ing with antiosteopontin antibody, which is secreted

by proximal and distal tubular cells and the cells of

the thin ascending loop of Henle, stained the tubularsections. Immunohistochemical staining for alkaline

phosphatase stained proximal tubule-like structures.

Uniform staining for bronectin in the extracellular

matrix of newly formed tubes was observed. The

uid collected from the reservoir was yellow and

contained 66 mg/dl uric acid (as compared to 2 mg/dl

in plasma) suggesting that these tubules are capable

of unidirectional secretion and concentration of uric

acid. The creatinine assay performed on the collected

uid showed an 8.2-fold increase in concentration, as

compared to serum. These results demonstrated thatsingle cells from multicellular structures can become

organized into functional renal units that are able to

excrete high levels of solutes through a urine-like

uid [46].

To determine whether renal tissue could be formed

using an alternative cell source, nuclear transplanta-

tion (therapeutic cloning) was performed to generate

histocompatible tissues, and the feasibility of engi-

neering syngeneic renal tissues in vivo using these

cloned cells was investigated [25]. Nuclear material

from bovine dermal broblasts was transferred intounfertilized enucleated donor bovine eggs. Renal

cells from the cloned embryos were harvested, ex-

panded in vitro, and seeded onto three-dimensional

renal devices (Fig. 60.1a). The devices were im-

planted into the back of the same steer from which

Fig. 60.1ac Formation of functional renal tissue in vivo. aRenal device. bTissue-engineered renal unit shows the accumu-lation of urine-like uid. cThere was a clear unidirectional continuity between the mature glomeruli, their tubules, and the

polycarbonate membrane



5/7

the cells were cloned, and were retrieved 12 weeks

later. This process produced functioning renal units.

Urine production and viability were demonstrated

after transplantation back into the nuclear donor

animal (Fig. 60.1b). Chemical analysis suggested

unidirectional secretion and concentration of urea

nitrogen and creatinine. Microscopic analysis re-vealed formation of organized glomeruli and tubular

structures (Fig. 60.1c). Immunohistochemical and

RT-PCR analysis conrmed the expression of renal

mRNA and proteins, whereas delayed-type hyper-

sensitivity testing and in vitro proliferative assays

showed that there was no rejection response to the

cloned cells. This study indicates that the cloned re-

nal cells are able to form and organize into functional

tissue structures which are genetically the same as

the host. Generating immune-compatible cells using

therapeutic cloning techniques is feasible and may beuseful for the engineering of renal tissues for autolo-

gous applications.

In our previous study, we showed that renal cells

seeded on synthetic renal devices attached to a col-

lecting system are able to form functional renal units

that produce urine-like uid. However, a naturally

derived tissue matrix with existing three-dimensional

kidney architecture would be preferable, because it

would allow for transplantation of a larger number

of cells, resulting in greater renal tissue volumes.

Thus, we developed an acellular collagen-basedkidney matrix, which is identical to the native renal

architecture. In a subsequent study we investigated

whether these collagen-based matrices could accom-

modate large volumes of renal cells and form kidney

structures in vivo [47].

Acellular collagen matrices, derived from por-

cine kidneys, were obtained through a multistep de-

cellularization process. During this process, serial

evaluation of the matrix for cellular remnants was

performed using histochemistry, scanning electron

microscopy (SEM) and RT-PCR. Mouse renal cellswere harvested, grown, and seeded on 80 of the de-

cellularized collagen matrices at a concentration of

30106 cells/ml. Forty cell-matrix constructs grown

in vitro were analyzed 3 days, 1, 2, 4, and 6 weeks af-

ter seeding. The remaining 40 cell-containing matri-

ces were implanted in the subcutaneous space of 20

athymic mice. The animals were sacriced 3 days, 1,

2, 4, 8, and 24 weeks after implantation for analyses.

Gross, SEM, histochemical, immunocytochemical,

and biochemical analyses were performed.

Scanning electron microscopy and histologic ex-

amination conrmed the acellularity of the processed

matrix. RT-PCR performed on the kidney matrices

demonstrated the absence of any RNA residues. Re-

nal cells seeded on the matrix adhered to the innersurface and proliferated to conuency 7 days after

seeding, as demonstrated by SEM. Histochemical

and immunocytochemical analyses performed using

H & E, periodic acid Schiff, alkaline phosphatase,

antiosteopontin and anti-CD-31 identied stromal,

endothelial, and tubular epithelial cell phenotypes

within the matrix. Renal tubular and glomerulus-like

structures were observed 8 weeks after implantation.

MTT proliferation and titrated thymidine incorpo-

ration assays performed 6 weeks after cell seeding

demonstrated a population increase of 116% and92%, respectively, as compared to the 2-week time

points. This study demonstrates that renal cells are

able to adhere to and proliferate on the collagen-

based kidney matrices. The renal cells reconstitute

renal tubular and glomeruli-like structures in the

kidney-shaped matrix. The collagen-based kidney

matrix system seeded with renal cells may be useful

in the future for augmenting renal function.

However, creation of renal structures without the

use of an articial device system would be prefera-

ble, as implantation procedures are invasive and mayresult in unnecessary complications. We also inves-

tigated the feasibility of creating three-dimensional

renal structures for in situ implantation within the na-

tive kidney tissue. Primary renal cells from 4-week-

old mice were grown and expanded in culture. These

renal cells were labeled with uorescent markers and

injected into mouse kidneys in a collagen gel for in

vivo formation of renal tissues. Collagen injection

without cells and sham-operated animals served as

controls. In vitro reconstituted renal structures and

in vivo implanted cells were retrieved and analyzed.The implanted renal cells formed tubular and glom-

erular structures within the kidney tissue, as con-

rmed by the uorescent markers. There was no

evidence of renal tissue formation in the control and

the sham-operated groups. These results demonstrate

that single renal cells are able to reconstitute kidney

structures when placed in a collagen-based scaffold-

ing system. The implanted renal cells are able to



6/7

self assemble into tubular and glomerular structures

within the kidney tissue (Fig. 60.2). These ndingssuggest that this system may be the preferred ap-

proach to engineer functional kidney tissues for the

treatment of end stage renal disease.

60.5

Summary

The increasing demand for renal transplantation,combined with the critical shortage of donor organs,

has ignited intense interest in seeking alternative

treatment modalities. Cell-based approaches have

been proposed as a viable method for kidney tissue

regeneration. Various tissue engineering and regen-

erative medicine approaches that aim to achieve

functional intra- and extracorporeal kidney support

were presented in this chapter. Although the progress

in this area has been somewhat successful toward

regeneration of functional kidney tissue, clinical ap-

plication of this technology is still distant.The concept of renal cell transplantation has been

demonstrated on multiple occasions. It has been

shown that renal cells are able to reconstitute into

functional kidney tissues in vivo, but numerous chal-

lenges must be addressed and solved in order for

these techniques to be applied clinically. Some of

these challenges include the generation of a large tis-

sue mass that could augment systemic renal function,

the formation of adequate vascularization in the en-

gineered renal tissue, and the development of a reli-able renal failure model system for testing cell-based

technologies.

References

1. Amiel, G. E., Yoo, J. J., Atala, A.: Renal therapy using

tissue-engineered constructs and gene delivery. World J

Urol, 18: 71, 2000

2. Chazan, J. A., Libbey, N. P., London, M. R. et al.: The

clinical spectrum of renal osteodystrophy in 57 chronichemodialysis patients: a correlation between biochemi-

cal parameters and bone pathology ndings. Clin Neph-

rol, 35: 78, 1991

3. Cohen, J., Hopkin, J., Kurtz, J.: Infectious complications

after renal transplantation Philadelphia, WB Saunders,

1994

4. Frank, J., Engler-Blum, G., Rodemann, H. P. et al.: Hu-

man renal tubular cells as a cytokine source: PDGF-B,

GM-CSF and IL-6 mRNA expression in vitro. Exp Neph-

rol, 1: 26, 1993

5. Maack, T.: Renal handling of low molecular weight pro-

teins. Am J Med, 58: 57, 1975

6. Stadnyk, A. W.: Cytokine production by epithelial cells.

Faseb J, 8: 1041, 1994

7. Amiel, G. E., Yoo, J. J. and Atala, A.: Renal tissue en-

gineering using a collagen-based kidney matrix. Tissue

Engineering suppl, 2000

8. Amiel, G. E., Atala, A.: Current and future modalities for

functional renal replacement. Urol Clin North Am, 26:

235, 1999

9. Atala, A., Schlussel, R. N., Retik, A. B: Renal cell growth

in vivo after attachment to biodegradable polymer scaf-

folds. J Urol, 153, 1995

Fig. 60.2a,b Reconstitution of kidney structures. The implanted renal cells self assembled into (a) glomerular and (b) tubularstructures within the kidney tissue



7/7

10. Atala, A.: Tissue engineering in the genitourinary sys-

tem. Vol chap 8, 1997

11. Atala, A.: Future perspectives in reconstructive surgery

using tissue engineering. Urol Clin North Am, 26: 157,

1999

12. Humes, H. D., Bufngton, D. A., MacKay, S. M. et al.:

Replacement of renal function in uremic animals with a

tissue-engineered kidney. Nat Biotechnol, 17: 451, 1999

13. Humes, H. D., Fissell, W. H., Weitzel, W. F. et al.: Meta-bolic replacement of kidney function in uremic animals

with a bioarticial kidney containing human cells. Am J

Kidney Dis, 39: 1078, 2002

14. Ikarashi, K., Li, B., Suwa, M. et al.: Bone marrow cells

contribute to regeneration of damaged glomerular en-

dothelial cells. Kidney Int, 67: 1925, 2005

15. Kale, S., Karihaloo, A., Clark, P. R. et al.: Bone marrow

stem cells contribute to repair of the ischemically injured

renal tubule. J Clin Invest, 112: 42, 2003

16. Lin, F., Cordes, K., Li, L. et al.: Hematopoietic stem cells

contribute to the regeneration of renal tubules after renal

ischemia-reperfusion injury in mice. J Am Soc Nephrol,

14: 1188, 2003

17. Lin, F., Moran, A., Igarashi, P.: Intrarenal cells, not bone

marrow-derived cells, are the major source for regen-

eration in postischemic kidney. J Clin Invest, 115: 1756,

2005

18. Prockop, D. J.: Marrow stromal cells as stem cells for

nonhematopoietic tissues. Science, 276: 71, 1997

19. Yokoo, T., Ohashi, T., Shen, J. S. et al.: Human mesen-

chymal stem cells in rodent whole-embryo culture are

reprogrammed to contribute to kidney tissues. Proc Natl

Acad Sci U S A, 102: 3296, 2005

20. Carley, W. W., Milici, A. J., Madri, J. A.: Extracellular

matrix specicity for the differentiation of capillary en-

dothelial cells. Exp Cell Res, 178: 426, 1988

21. Horikoshi, S., Koide, H., Shirai, T.: Monoclonal antibod-ies against laminin A chain and B chain in the human and

mouse kidneys. Lab Invest, 58: 532, 1988

22. Humes, H. D., Cieslinski, D. A.: Interaction between

growth factors and retinoic acid in the induction of kid-

ney tubulogenesis in tissue culture. Exp Cell Res, 201: 8,

1992

23. Milici, A. J., Furie, M. B., Carley, W. W.: The formation

of fenestrations and channels by capillary endothelium in

vitro. Proc Natl Acad Sci U S A, 82: 6181, 1985

24. Schena, F. P.: Role of growth factors in acute renal fail-

ure. Kidney Int Suppl, 66: S11, 1998

25. Lanza, R. P., Chung, H. Y., Yoo, J. J. et al.: Generation

of histocompatible tissues using nuclear transplantation.

Nat Biotechnol, 20: 689, 200226. Gupta, S., Verfaillie, C., Chmielewski, D. et al.: A role

for extrarenal cells in the regeneration following acute

renal failure. Kidney Int, 62: 1285, 2002

27. Ito, T., Suzuki, A., Imai, E. et al.: Bone marrow is a res-

ervoir of repopulating mesangial cells during glomerular

remodeling. J Am Soc Nephrol, 12: 2625, 2001

28. Iwano, M., Plieth, D., Danoff, T. M. et al.: Evidence that

broblasts derive from epithelium during tissue brosis.

J Clin Invest, 110: 341, 2002

29. Poulsom, R., Forbes, S. J., Hodivala-Dilke, K. et al.:

Bone marrow contributes to renal parenchymal turnover

and regeneration. J Pathol, 195: 229, 2001

30. Rookmaaker, M. B., Smits, A. M., Tolboom, H. et al.:

Bone-marrow-derived cells contribute to glomerular en-

dothelial repair in experimental glomerulonephritis. Am

J Pathol, 163: 553, 2003

31. Folkman, J., Hochberg, M.: Self-regulation of growth in

three dimensions. J Exp Med, 138: 745, 197332. Atala, A., Bauer, S. B., Soker, S. et al.: Tissue-engineered

autologous bladders for patients needing cystoplasty.

Lancet, 367: 1241, 2006

33. El-Kassaby, A. W., Retik, A. B., Yoo, J. J. et al.: Urethral

stricture repair with an off-the-shelf collagen matrix. J

Urol, 169: 170, 2003

34. Oberpenning, F., Meng, J., Yoo, J. J. et al.: De novo re-

constitution of a functional mammalian urinary bladder

by tissue engineering. Nat Biotechnol, 17: 149, 1999

35. Tachibana, M., Nagamatsu, G. R., Addonizio, J. C.: Ure-

teral replacement using collagen sponge tube grafts. J

Urol, 133: 866, 1985

36. Freed, L. E., Vunjak-Novakovic, G., Biron, R. J. et al.:

Biodegradable polymer scaffolds for tissue engineering.

Biotechnology (N Y), 12: 689, 1994

37. Hubbell, J. A., Massia, S. P., Desai, N. P. et al.: Endothe-

lial cell-selective materials for tissue engineering in the

vascular graft via a new receptor. Biotechnology (N Y),

9: 568, 1991

38. Mooney, D. J., Mazzoni, C. L., Breuer, C. et al.: Stabi-

lized polyglycolic acid bre-based tubes for tissue engi-

neering. Biomaterials, 17: 115, 1996

39. Wald, H. L., Sarakinos, G., Lyman, M. D. et al.: Cell

seeding in porous transplantation devices. Biomaterials,

14: 270, 1993

40. Dekel, B., Burakova, T., Arditti, F. D. et al.: Human

and porcine early kidney precursors as a new source fortransplantation. Nat Med, 9: 53, 2003

41. Steer, D. L., Bush, K. T., Meyer, T. N. et al.: A strategy

for in vitro propagation of rat nephrons. Kidney Int, 62:

1958, 2002

42. Rogers, S. A., Lowell, J. A., Hammerman, N. A. et al.:

Transplantation of developing metanephroi into adult

rats. Kidney Int, 54: 27, 1998

43. Hammerman, M. R.: Transplantation of embryonic kid-

neys. Clin Sci (Lond), 103: 599, 2002

44. Rogers, S. A., Powell-Braxton, L., Hammerman, M. R.:

Insulin-like growth factor I regulates renal development

in rodents. Dev Genet, 24: 293, 1999

45. Fung, L. C. T., Elenius, K., Freeman, M., Donovan, M.

J., Atala, A.: Reconstitution of poor EGFr-poor renalepithelial cells into tubular structures on biodegradable

polymer scaffold. Pediatrics, 98 (Suppl): S631, 1996

46. Yoo, J. J., Ashkar, S., Atala, A.: Creation of functional

kidney structures with excretion of kidney-like uid in

vivo. Pediatrics, 98S: 605, 1996

47. Yoo, J. J., Atala, A.: A novel gene delivery system us-

ing urothelial tissue engineered neo-organs. J Urol, 158:

1066, 1997


Engineering Renal

Documents

Transcript of Engineering Renal