Biomedical subjects

H Uludag

Publications and source records attributed to H Uludag.

At least 19 recordsLinked to original sources

PubMed2001

Engineering temperature-sensitive poly(N-isopropylacrylamide) polymers as carriers of therapeutic proteins.

This study was carried out to engineer N-isopropylacrylamide (NiPAM) polymers that contain protein-reactive N-acryloxysuccinimide (NASI) and hydrophobic alkylmethacrylates (AMAs). These thermoreversible, protein-conjugating polymers hold potential for retention of therapeutic proteins at an application site where tissue regeneration is desired. The lower critical solution temperatures (LCST) of the polymers were effectively controlled by the AMA mole content. The AMAs with longer side-chains were more effective in lowering the LCST. Polymers without NASI exhibited a stable LCST in phosphate buffer and in serum over a 10-day study period. The LCST of polymers containing NASI was found to increase over time in phosphate buffer, but not in serum-containing medium. The LCST increase in phosphate buffer was proportional to the AMA content. The feasibility of localizing a therapeutic protein, recombinant human bone morphogenetic protein-2 (rhBMP-2), to a site of application was explored in a rat intramuscular injection model. The results indicated that polymers capable of conjugating to rhBMP-2 were most effective in localizing the protein irrespective of the LCST (13-25 degrees C). For polymers with no NASI groups, a lower LCST resulted in a better rhBMP-2 localization. We conclude that thermosensitive polymers can be engineered for delivery of therapeutic proteins to improve their therapeutic efficacy.

Acrylic Resins↗

PubMed2001

Effect of molecular weight of thermoreversible polymer on in vivo retention of rhBMP-2.

To investigate the effect of polymer molecular weight (MW) on rhBMP-2 delivery by thermoreversible polymers, four polymers with similar lower critical solution temperatures (20 degrees -22 degrees C) but different MWs were studied. Thermoreversible polymers were based on N-isopropylacrylamide (NiPAM), ethyl methacrylate (EMA), and N-acryloxysuccinimide (NASI), and had MWs of either approximately 49 kDa or approximately 400 kDa. The NASI content was either 0 or 1-1.6%. High MW polymers, irrespective of their NASI content, formed a stable gel with significantly lower water uptake and exhibited a dense micelle with average pore size smaller than the low MW polymers. NiPAM/EMA polymers without NASI did not conjugate with recombinant human bone morphogenetic protein-2 (rhBMP-2). NiPAM/EMA polymers containing NASI, however, gave conjugation with rhBMP-2. For polymers without NASI, a high MW was essential for rhBMP-2 retention when injected intramuscularly in Sprague-Dawley rats. For NASI-containing polymers, the MW of the polymer did not make a significant difference because rhBMP-2 retention was equivalent for different size polymers. We conclude that polymer MW affects rhBMP-2 retention in vivo in polymers designed for physical entrapment of rhBMP-2, but not in polymers designed for chemical conjugation with rhBMP-2.

Animals↗

PubMed2001

Growth factor delivery for bone tissue engineering.

Bone is a dynamic tissue that undergoes significant turnover during the life cycle of an individual. Despite having a significant regenerative capability, trauma and other pathological scenarios commonly require therapeutic intervention to facilitate the healing process. Bone tissue engineering, where cellular and biological processes at a site are deliberately manipulated for a therapeutic outcome, offers a viable option for the treatment of skeletal diseases. In this review paper, we aim to provide a brief synopsis of cellular and molecular basis of bone formation that are pertinent to current efforts of bone healing. Different approaches for engineering bone tissue were presented with special emphasis on the use of soluble (diffusible) therapeutic agents to accelerate bone healing. The latter agents have been used for both local bone repair (i.e. introduction of agents directly to a site of repair) as well as systemic bone regeneration (i.e. delivery for regeneration throughout the skeletal system). Critical drug delivery and targeting issues pertinent for each mode of bone regeneration are provided. In addition, future challenges and opportunities in bone tissue engineering are proposed from the authors' perspective.

Bone Morphogenetic Proteins↗

PubMed2001

Delivery systems for BMPs: factors contributing to protein retention at an application site.

BACKGROUND: Recombinant human bone morphogenetic proteins (rhBMPs) are being tested in clinical studies for their capacity to elicit bone formation. Biomaterials used in delivery systems also play a critical role in supporting the osteoinductive activity of BMPs, attributable to the controlled presentation of the BMPs to target cells. Despite extensive preclinical studies, the factors contributing to local rhBMP pharmacokinetics remain to be elucidated. METHODS: The rhBMP pharmacokinetics were studied in a rat subcutaneous implant and in an intramuscular injection model. In situ levels of rhBMPs were quantitated with use of 125I-labeled tracers. The effects of protein structural features and the nature of the biomaterial implant were explored. Osteoinduction by biomaterial+rhBMP combinations was assessed by a semiquantitative, histology-based bone score. RESULTS: With the use of rhBMP-2, rhBMP-4, and an N-truncated rhBMP-2, the protein isoelectric point was found critical for the initial retention of rhBMPs in an implant. Osteoinduction studies carried out in parallel indicated that rhBMPs with a higher implant retention elicited more bone formation. In the clinically used collagen+rhBMP-2 device, collagen crosslinking and sterilization were most influential in rhBMP-2 retention. To increase retention at an application site, thermoreversible polymers were engineered and shown to enhance local rhBMP-2 retention, especially by injectable delivery. CONCLUSIONS: Two critical components of an osteoinductive device--namely, the biomaterial and the rhBMP--were shown to influence local protein pharmacokinetics and osteoinductive activity of the device. Designer biomaterials can provide an additional mechanism to modulate local protein pharmacokinetics. CLINICAL RELEVANCE: These studies form the foundation of next-generation osteoinductive devices with improved potency at sites of desired bone regeneration and reduced side effects at other sites.

Animals↗

PubMed2000

Technology of mammalian cell encapsulation.

Entrapment of mammalian cells in physical membranes has been practiced since the early 1950s when it was originally introduced as a basic research tool. The method has since been developed based on the promise of its therapeutic usefulness in tissue transplantation. Encapsulation physically isolates a cell mass from an outside environment and aims to maintain normal cellular physiology within a desired permeability barrier. Numerous encapsulation techniques have been developed over the years. These techniques are generally classified as microencapsulation (involving small spherical vehicles and conformally coated tissues) and macroencapsulation (involving larger flat-sheet and hollow-fiber membranes). This review is intended to summarize techniques of cell encapsulation as well as methods for evaluating the performance of encapsulated cells. The techniques reviewed include microencapsulation with polyelectrolyte complexation emphasizing alginate-polylysine capsules, thermoreversible gelation with agarose as a prototype system, interfacial precipitation and interfacial polymerization, as well as the technology of flat sheet and hollow fiber-based macroencapsulation. Four aspects of encapsulated cells that are critical for the success of the technology, namely the capsule permeability, mechanical properties, immune protection and biocompatibility, have been singled out and methods to evaluate these properties were summarized. Finally, speculations regarding future directions of cell encapsulation research and device development are included from the authors' perspective.

Alginates↗

PubMed2000

Implantation of recombinant human bone morphogenetic proteins with biomaterial carriers: A correlation between protein pharmacokinetics and osteoinduction in the rat ectopic model.

This study was carried out to determine the effect of recombinant human bone morphogenetic protein (rhBMP) pharmacokinetics (PK) on rhBMP-induced osteoinductive activity. It was our working hypothesis that the PK of a rhBMP significantly affects its osteoinductive activity. The PK of various rhBMPs (rhBMP-2, rhBMP-4, rhBMP-6, and chemically modified rhBMP-2) implanted with four biomaterial carries (Helistat, hDBM, Osteograf/N, and Dexon) was determined using (125)I-labeled proteins in the rat ectopic assay. A select combination of rhBMP and carriers then was evaluated in the rat ectopic assay for osteoinductive activity using a semi-quantitative histologic scoring system. The results indicate that initial protein retention is dependent on protein isoelectric point (pI); proteins with a higher pI yielded a higher implant retention. Subsequent PK was not strongly dependent on the pI or on the carrier. Because of the difference in early retention, the rhBMP-carrier combinations exhibited a >100-fold difference in implant-retained protein dose. When rhBMP-2 and rhBMP-4 were implanted with the carriers, more rhBMP-2 was retained in an implant, and the osteoinductive potency of rhBMP-2 typically was higher than rhBMP-4 at low implantation doses. We conclude that protein pI plays a significant role in the local retention of implanted rhBMP and that higher retention yields a higher osteoinductive activity.

Amino Acid Sequence↗

PubMed1999

Biotinated bone morphogenetic protein-2: In vivo and in vitro activity.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) was biotinated, and the bioactivity of biotinated protein was assessed in vitro (alkaline phosphate induction in limb bud cells) and in vivo (osteoinduction in the rat ectopic assay). Amino-biotinated rhBMP-2 exhibited an increase in bioactivity whereas carboxy-biotinated rhBMP-2 did not exhibit any changes in bioactivity in vitro. Avidin inhibited the bioactivity of amino-biotinated but not carboxyl-biotinated rhBMP-2. Both amino- and carboxy-modified rhBMP-2 induced bone at an equivalent level to that of unmodified rhBMP-2 in vivo. The presence of avidin did not affect the osteoinductive activity of both types of biotinated rhBMP-2. The overall results indicated that binding to a large protein, avidin, might affect rhBMP-2 activity in vitro depending on the binding site; however, in vivo activity was unaffected by the avidin binding.

Animals↗

PubMed1999

Characterization of absorbable collagen sponges as rhBMP-2 carriers.

For clinical use recombinant human bone morphogenetic protein (rhBMP-2) is soaked onto an absorbable collagen sponge (ACS) for bone regeneration. Therefore, loss of rhBMP-2 upon mechanical handling during implantation and a potential effect of the carrier on in vivo retention is of interest. The interactions between drug and carrier were looked at from the application mode and the amount of protein which can be mechanically expressed from the combination was investigated. The results indicated that rhBMP-2 binds to the collagen system. The most hydrophilic double extended homodimer showed the least binding affinity to ACS. By extending the waiting time between soaking and implantation, protein incorporation could be increased. In addition, the amount of rhBMP-2 which could be expressed was reduced by heavier ACS material and allowed for a shorter waiting period, especially at lower rhBMP-2 concentration. Crosslinking of ACS with formaldehyde led to reduced binding of rhBMP-2 to collagen either by direct hindrance of binding or reduction in swelling and number of binding sites available. Higher product pH or anion concentration enabled to increase rhBMP-2 incorporation but was limited by the potential precipitation of rhBMP-2. Despite a variety of chemical changes of ACS by ethylene oxide sterilization incorporation was not changed significantly. The in vivo release kinetics of 125I-rhBMP-2 from the collagen sponge were studied using a rat ectopic implant model. The ACS/rhBMP-2 systems tested demonstrated small, but significant differences in the in vivo retention of rhBMP-2. Consequently, it is important to have as little variability in pH, anion concentration, crosslinking and ACS mass as possible to achieve consistent or maximum binding and to avoid rhBMP-2 precipitation. Furthermore, these characteristics can be important for other in vivo applications.

Absorbable Implants↗

PubMed1999

Characterization of absorbable collagen sponges as recombinant human bone morphogenetic protein-2 carriers.

For clinical use recombinant human bone morphogenetic protein-2 (rhBMP-2) is soaked onto an absorbable collagen sponge (ACS) for bone regeneration. Therefore, loss of rhBMP-2 upon mechanical handling during implantation and a potential effect of the carrier on in vivo retention is of interest. The interactions between drug and carrier were looked at from the application mode and the amount of protein which can be mechanically expressed from the combination was investigated. The results indicated that rhBMP-2 binds to the collagen system. The most hydrophilic double extended homodimer showed the least binding affinity to ACS. By extending the waiting time between soaking and implantation, protein incorporation could be increased. In addition, the amount of rhBMP-2 which could be expressed was reduced by heavier ACS material and allowed for a shorter waiting period, especially at lower rhBMP-2 concentration. Crosslinking of ACS with formaldehyde led to reduced binding of rhBMP-2 to collagen either by direct hindrance of binding or reduction in swelling and number of binding sites available. Higher product pH or anion concentration enabled to increase rhBMP-2 incorporation but was limited by the potential precipitation of rhBMP-2. Despite a variety of chemical changes of ACS by ethylene oxide sterilization incorporation was not changed significantly. The in vivo release kinetics of (125)I-rhBMP-2 from the collagen sponge were studied using a rat ectopic implant model. The ACS/rhBMP-2 systems tested demonstrated small but significant differences in the in vivo retention of rhBMP-2. Consequently, it is important to have as little variability in pH, anion concentration, crosslinking, and ACS mass as possible to achieve consistent or maximum binding and to avoid rhBMP-2 precipitation. Furthermore, these characteristics can be important for other in vivo applications.

Absorbable Implants↗

PubMed1999

rhBMP-collagen sponges as osteoinductive devices: effects of in vitro sponge characteristics and protein pI on in vivo rhBMP pharmacokinetics.

Osteoinductive devices, comprised of biodegradable collagen scaffolds and recombinant human Bone Morphogenetic Proteins (rhBMPs), are being currently pursued for local bone induction. To better understand the biological performance of such devices, we have carried out a series of studies to investigate the effects of sponge properties and protein structural features on the pharmacokinetics of implanted rhBMPs. The results indicated little dependence of the rhBMP-2 pharmacokinetics on the in vitro determined sponge properties. The protein isoelectric point (pI), on the other hand, was found to significantly affect the initial implant retention of rhBMPs, but not the subsequent pharmacokinetics. A 100-fold difference in the implant-retained dose could be observed depending on the type of rhBMP implanted. We conclude that protein structural features are important variables controlling in vivo pharmacokinetics of rhBMPs, and possibly the osteoinductive potency of the devices.

Biocompatible Materials↗

PubMed1999

Characterization of rhBMP-2 pharmacokinetics implanted with biomaterial carriers in the rat ectopic model.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a member of the bone morphogenetic protein family involved in de novo bone induction. Successful use of rhBMP-2 requires implantation with a biomaterial which can act as a scaffold for cell invasion for osteoinduction and retains rhBMP-2 at a site of implantation. This study was carried out to characterize rhBMP-2 pharmacokinetics from a variety of biomaterial carriers in a rat ectopic model. Retention of rhBMP-2 within carriers after 3 h was variable among the carriers (range, 75-10%), with collagenous sponges retaining the highest fraction of implanted dose. A gradual loss of rhBMP-2 was subsequently observed, the kinetics of which was strongly dependent on the implanted carrier. Collagenous carriers were observed to lose rhBMP-2 gradually from the implant site, whereas some of the mineral-based carriers retained a fraction of implanted rhBMP-2 within the implants. These differences in protein pharmacokinetics among carriers, in addition to their physicochemical nature, are expected to affect the biological activity of implanted rhBMP-2.

Animals↗

PubMed1999

Bone regeneration with recombinant human bone morphogenetic protein-2 (rhBMP-2) using absorbable collagen sponges (ACS): influence of processing on ACS characteristics and formulation.

The effects of variability in three parameters (mass, cross-linking with CH2O, and EtO sterilization) of three surgically implantable absorbable collagen sponges (ACS) were studied. Sponges soaked with recombinant human bone morphogenetic protein-2 (rhBMP-2) solution were analyzed for pH, conductivity, and rhBMP-2 precipitation. A method using trinitrobenzenesulfonic acid was developed to quantify the free amino groups of the collagen sponge. With up to 240 min exposure to CH2O, the amount of free amino groups was reduced to 80%. In comparison, the denaturation temperature as determined by differential scanning calorimetry (DSC) after the sponges were soaked with phosphate-buffered saline, increased from 48 to 55 degrees C, indicating stronger interactions due to cross-linking. Subsequent sterilization with EtO caused a marked decrease in the amount of free amino groups (approximately 33% of nonsterilized controls) independent of previous CH2O treatment. However, the denaturation temperature was on average 5 degrees C lower in sterilized sponges than in nonsterilized material. In contrast to CH2O exposure, the strong reaction with EtO appeared to weaken the collagen structure. Resistance of the sponge to collagenase correlated with the degree of collagen cross-linking but was slightly reduced by sterilization. In addition, the pH of ACS soaked with water was substantially increased by sterilization. Protein precipitation was a function of pH and salt concentration but there was no effect due to collagen alone. Results indicated that ACS weight has to be limited to avoid rhBMP-2 precipitation.

Absorbable Implants↗

PubMed1999

Carrier systems for bone morphogenetic proteins.

Bone deficits can regenerate inherently, although when the amount of bone loss exceeds a critical limit, pseudarthrosis and fibrosis occur. Therapeutic intervention either with an autograft or allogeneic bank bone are traditional options to promote regeneration to overcome critical limits. However, liabilities with traditional treatments have inspired investigators to develop alternatives, such as combinations of biomimetic scaffolds and osteogenic regulatory molecules. The class of osteogenic regulatory molecules known as the bone morphogenetic proteins has several members that stimulate bone regeneration. Therapeutic applications of bone morphogenetic proteins require a well characterized carrier system to ensure safe and effective presentation at the implant site. Several carrier systems have been used to evaluate the sustained release and implant retention of recombinant human bone morphogenetic protein-2. The carrier systems used in this study include type I collagen, poly(D,L-lactide), and deorganified bovine bone. Pharmacokinetics of recombinant human bone morphogenetic protein-2 released from these systems were characterized in the rat ectopic assay. Pharmacokinetics were influenced by the implant carrier. For example, sustained release occurred with the collagen sponge. The recombinant human bone morphogenetic protein-2 from deorganified bovine bone resulted in a burst release at the first collection interval, but thereafter, appeared to bind irreversibly to the morphogen. The poly (D,L-lactide) systems showed a dose dependent sustained release pattern. These results indicate the physicochemical characteristics of a carrier system for recombinant human bone morphogenetic protein-2 impact the release kinetics and may have a profound influence on clinical outcome.

Animals↗

PubMed1999

Establishing an immortalized human osteoprecursor cell line: OPC1.

The present studies evaluated the feasibility of establishing a conditionally immortalized osteoprecursor cell line derived from human fetal bone tissue. Primary cultures were transfected with a plasmid in which the Mx-1 promoter drives the expression of SV40 T-antigen when activated by human A/D interferon. Several neomycin (G418)-resistant colonies were characterized for cell growth and alkaline phosphatase (ALP) enzyme activity. The clone, designated OPC1 (osteoblastic precursor cell line 1), which exhibited the highest ALP enzyme activity at passage 10 (P10), was selected for additional osteogenic phenotypic characterization. Reverse transcription-polymerase chain reaction (RT-PCR) phenotyping revealed abundant mRNA for osteocalcin (OC), osteonectin (ON), osteopontin (OP), parathyroid hormone receptor (PTHr), ALP, and procollagen type I (ProI). In addition, the levels of quantitative RT-PCR product of ON, OP, PTHr, and ProI mRNAs exhibited a marked up-regulation when maintained in medium containing an osteogenic supplement (OS). The ability to stimulate osteogenic differentiation was characterized in postconfluent OPC1 cells maintained in tissue culture medium supplemented with recombinant human bone morphogenetic protein-2 (rhBMP-2) either with or without an OS. All treatment groups exhibited a striking up-regulation of ALP enzyme activity that coincided with ALP histochemical observations. Postconfluent cells also exhibited the ability to form mineralized nodules under all treatments (confirmed by von Kossa histochemical staining and calcium deposition). An enzyme immunosorbent assay (EIA) was utilized to measure intact human OC from the OPC1 line under the various treatments. Abundant OC was evident in the tissue culture medium indicating de novo sythesis and release from the OPC1 line under appropriate conditions. The clonal human-derived OPC1 line represents a homogeneous osteogenic cell line that not only has maintained a consistent bone phenotype from P10 to at least P30, but has also exhibited the capacity to generate programmed differentiation in the presence of low dose rhBMP-2 (10 ng/ml). Thus, the OPC1 line is a human-derived osteoprecursor that provides a sensitive in vitro cell culture system to evaluate bone development, cell/biomaterial interactions, and may be a useful screen for putative bone differentiating factors.

Alkaline Phosphatase↗

PubMed1998

Sustained release emphasizing recombinant human bone morphogenetic protein-2.

Bone homeostasis is a dynamic process involving a myriad of cells and substrates modulated by regulatory signals such as hormones, growth and differentiating factors. When this environment is damaged, the regenerative sequalae follows a programmed pattern, and the capacity for successful recovery is often dependent on the extent of the injury. Many bony deficits that are excessively traumatic will not result in complete recovery and require therapeutic intervention(s) such as autografting or grafting from banked bone. However, for numerous reasons, an unacceptably high rate of failure is associated with these conventional therapies. Thus, alternative approaches are under investigation. A class of osteogenic regulatory molecules, the bone morphogenetic proteins (BMPs), have been isolated, cloned and characterized as potent supplements to augment bone regeneration. Optimizing a therapeutic application for BMPs may be dependent upon localized sustained release which in kind relies on a safe and well characterized carrier system. This review will discuss the current status of BMPs in bone regeneration and specifically will present the potential for a clinical therapeutic role of recombinant human BMP-2 sustained release carrier systems.

Journal Article↗

PubMed1993

Microencapsulated human hepatoma (HepG2) cells: in vitro growth and protein release.

The feasibility of a microencapsulation process ultimately for cell transplantation was investigated by encapsulating human hepatoma (HepG2) cells in hydroxyethyl methacrylate-methyl methacrylate (HEMA-MMA) membranes through an interfacial precipitation process. Changes in viability and metabolic activity as well as protein secretion by the encapsulated cells were studied in vitro. When encapsulated at either low or high density (1 or 5 x 10(6) cells/mL, respectively), HepG2 cells retained their active metabolic state and/or proliferated during the initial 1-week period, after which a significant drop in cell viability was obtained. Encapsulation of a biological attachment substrate, Matrigel, along with the cells, however, resulted in rapid proliferation in both low and high density capsules with prolonged maintenance of an active metabolic state. The secretion of four model proteins (alpha 1-acid glycoprotein, alpha 1-antitrypsin, haptaglobin and fibrinogen) was demonstrated during the 2-week study period for the Matrigel encapsulated cells. Furthermore, the encapsulated cells remained responsive to interleukin 6 (IL6), a physiological stimulator of plasma protein secretion, as determined by the elevated secretion of haptaglobin in response to IL6 treatment. We conclude that HEMA-MMA capsules, in the presence of an attachment substrate, provide a suitable environment for the growth and expression of differentiated functions of encapsulated hepatoma cells.

Biocompatible Materials↗

PubMed1990

Colorimetric assay for cellular activity in microcapsules.

Cellular activity in microcapsules was determined by a simple colorimetric assay, based on the cellular transformation of a tetrazolium salt, 3-(4,5-dimethyl-thiazol-2-yl)-2,5- diphenyl-tetrazolium bromide, into an insoluble formazan which was quantified in a spectrophotometer. The results showed that when encapsulated Chinese hamster ovary fibroblasts were exposed to the tetrazolium salt containing tissue culture medium, the formazan crystals were formed inside the poly(hydroxyethyl methacrylate-methyl methacrylate) microcapsules; capsules containing no cells or dead cells formed no formazan. A detectable amount of formazan was readily obtained even from single capsules. Formazan production was dependent on the incubation time, but not on the amount of added reagent. Capsules from a high cell-density encapsulation (4 X 10(6) cells/ml) formed more formazan than capsules from a low cell-density (4 X 10(5) cells/ml) encapsulation, suggesting a positive correlation between the cell density and tetrazolium transformation in microcapsules. The tetrazolium assay indicated the maintenance of cellular activity but slow, if any, proliferation in microcapsules over a 2 wk testing period.

Animals↗

PubMed1990

Transport functions in a bioartificial kidney under uremic conditions.

A bioartifical kidney, a confluent monolayer of renal tubular cells attached to a permselective synthetic membrane, may some day substitute for the failing renal function. In such a device, the cells would have to exhibit transport properties when exposed to uremic plasma. To test the feasibility of a bioartificial kidney, LLC-PK1 cells derived from the proximal tubule were grown to confluence on microporous, cellulose nitrate membranes and transepithelial transport of inulin, glucose and tetraethylammonium (TEA) was investigated with standard tissue culture medium and with the hemofiltrate obtained from a uremic patient. Inulin, which is neither reabsorbed nor secreted by renal epithelial cells, did not diffuse through the LLC-PK1 monolayer in either tissue culture fluid or hemofiltrate. Glucose was preferentially reabsorbed and TEA was preferentially secreted in both media. In hemofiltrate, LLC-PK1 cells reabsorbed glucose at the same rate as in tissue culture fluid but secreted TEA at a significantly higher rate. This difference was related to the pH of the fluids since it was abolished by correction to the same pH value. For both solutes, the passive transepithelial leakage was significantly lower in hemofiltrate. We conclude that LLC-PK1 cells retain their reabsorbtive and secretory transport characteristics under uremic conditions.

Animals↗