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Autologous Chondrocyte Injection — Historical Bulking Research

Auricular chondrocytes expanded in culture and mixed with alginate were investigated as a living bulking implant for pediatric vesicoureteral reflux (VUR) and female stress urinary incontinence (SUI). The early studies showed feasibility; their uncontrolled designs, limited populations, relapse, and late calcification do not establish a routine contemporary treatment. This page is most useful when assessing patients who received these implants years ago.[1][2][3][4]

Biological Concept and Early Experiments​

The proposed mechanism combined immediate gel bulk with subsequent cartilage formation. The original 1993 experiment used bovine articular chondrocytes in athymic mice, not human auricular cartilage: cartilage formed at 34/36 experimental injection sites, with no migration or granuloma found during the experiment. A subsequent study used autologous ear chondrocytes in four mini-pigs with surgically created reflux; treated ureters showed reflux resolution while contralateral controls remained refluxing.[5][6]

These are preclinical observations. They do not prove lifelong implant stability, zero immunogenicity, or absence of migration in humans. A cell's autologous origin also does not remove risks associated with the scaffold, processing, injection, or donor-site procedure.

How the Clinical Studies Were Performed​

The pediatric studies used a staged approach: posterior auricular cartilage harvest, approximately six weeks of cell expansion, then endoscopic subureteral injection. Stored cells could be used for retreatment. The female SUI study instead used one outpatient injection just distal to the bladder neck. These descriptions explain the research protocols; they are not preparation instructions for current clinical use.[1][2][3]

Clinical Evidence​

StudyPopulation and assessmentResults and interpretation
Diamond and Caldamone 199929 children, 46 grade II–IV refluxing ureters; cystography at three monthsFirst injection corrected 26/46 ureters (57%). A second injection corrected 12/19 retreated ureters (63%), bringing total correction to 38/46 ureters and 24/29 children (83%). The 63% figure is success among retreated ureters, not cumulative success.[1]
Caldamone and Diamond 2001Follow-up report from the pediatric programAt one year, reflux correction was reported in 32/46 ureters (70%) and 19/29 children (65%). Follow-up after retreatment of three ureters was unavailable. Cystoscopy in failures showed mound volume loss and displacement; the early response did not ensure sustained reflux control.[2]
Bent 2001Uncontrolled multicenter study; 32 women with ISD; single treatmentIncontinence grading at 12 months found 16 dry and ten improved, giving 50% dry and 81.3% combined dry/improved. These are distinct endpoints; without a comparator, they do not show superiority or equivalence to a marketed bulking agent or sling.[3]

The studies concern different sites, diseases, and endpoints. Their rates should not be combined into a single success estimate or compared with unrelated modern cohorts without accounting for selection, repeat treatment, and follow-up.

Mound Volume and Imaging​

Paltiel's sonographic study included 32 children and 56 treated ureters, but the paired volume analysis was limited to 14 children with both early and late scans. Mean mound volume fell from 0.56 to 0.37 cm³ (approximately 34%; p=0.004) over mean imaging intervals of 1.4 and 12 months. Absent or multilobed mounds were associated with persistent reflux. The association does not prove that volume loss is the sole cause of every recurrence.[7]

Transient collecting-system dilatation was reported and resolved in that study. This small series cannot establish a universal absence of obstruction.[7]

Late Calcification and Prior-Implant Assessment​

In Gargollo's single-center cohort, 10/27 patients (37%) developed mound calcification. Overall median follow-up was nine years; calcification was first identified at a median 2.1 years after injection, not necessarily at year nine. Seven of the ten had hematuria with or without flank pain, and three were initially thought to have ureterovesical-junction stones. No hydroureteronephrosis was found in the patients with calcified mounds.[4]

The mechanism remained uncertain, and this cohort's event rate should not be applied to all patients or other injectables. A calcified mound can mimic a stone, but prior injection does not justify dismissing new hematuria, pain, infection, or obstruction. Retrieve earlier operative and imaging records and assess the current presentation.[4]

Three children in the 2001 follow-up underwent successful open reimplantation after failed injection. This supports feasibility in those cases, not a guarantee that all subsequent reconstruction is unaffected.[2]

Place in Current Practice​

The evidence retained here is historical, small, and predominantly uncontrolled. Culture expansion, staged intervention, variable durability, and incomplete long-term safety characterization distinguish it from an off-the-shelf implant. Other cell approaches, such as muscle-derived cell injection, are different interventions and do not validate auricular chondrocyte bulking. Current treatment decisions should follow the relevant VUR device hub or continence procedure hub, rather than the experimental protocols summarized here.[1][2][3][4]

See also: Historical Bulking Agents, Contigen, and Autologous Fat.

References​

1. Diamond DA, Caldamone AA. Endoscopic Correction of Vesicoureteral Reflux in Children Using Autologous Chondrocytes: Preliminary Results. The Journal of Urology. 1999;162(3 Pt 2):1185-1188. doi:10.1016/S0022-5347(01)68124-2

2. Caldamone AA, Diamond DA. Long-Term Results of the Endoscopic Correction of Vesicoureteral Reflux in Children Using Autologous Chondrocytes. The Journal of Urology. 2001;165(6 Pt 2):2224-2227. doi:10.1016/S0022-5347(05)66170-8

3. Bent AE, Tutrone RT, McLennan MT, et al. Treatment of Intrinsic Sphincter Deficiency Using Autologous Ear Chondrocytes as a Bulking Agent. Neurourology and Urodynamics. 2001;20(2):157-165. PubMed.

4. Gargollo PC, Paltiel HJ, Rosoklija I, Diamond DA. Mound Calcification After Endoscopic Treatment of Vesicoureteral Reflux With Autologous Chondrocytes — a Normal Variant of Mound Appearance? The Journal of Urology. 2009;181(6):2702-2708. doi:10.1016/j.juro.2009.02.053

5. Atala A, Cima LG, Kim W, et al. Injectable Alginate Seeded With Chondrocytes as a Potential Treatment for Vesicoureteral Reflux. The Journal of Urology. 1993;150(2 Pt 2):745-747. doi:10.1016/s0022-5347(17)35603-3

6. Atala A, Kim W, Paige KT, Vacanti CA, Retik AB. Endoscopic Treatment of Vesicoureteral Reflux With a Chondrocyte-Alginate Suspension. The Journal of Urology. 1994;152(2 Pt 2):641-643. doi:10.1016/s0022-5347(17)32671-x

7. Paltiel HJ, Diamond DA, Zurakowski D, Drubach LA, Atala A. Endoscopic Treatment of Vesicoureteral Reflux With Autologous Chondrocytes: Postoperative Sonographic Features. Radiology. 2004;232(2):390-397. doi:10.1148/radiol.2322030551