Composition for the delivery of live cells and methods of use thereof

a technology for live cells and liquid systems, applied in drug compositions, skeletal/connective tissue cells, metabolic disorders, etc., can solve the problems of difficult control of liquid systems within a particular area, risk of infection, invasive and painful procedures, etc., and achieve the effect of improving the primary therapeutic effect and shortening the time period

Inactive Publication Date: 2009-02-12
COSTANTINO HENRY R +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0012]In a particular embodiment, the composition comprising lives cells and biocompatible, biodegradable polymer microparticles further comprises a biologically active agent. In a preferred embodiment, the biologically active agent is incorporated into the microparticle. The biologically active agent can be, for example, factors which modulate cell growth, such as factors having tissue regeneration inductive properties, for example, growth factors and differentiating factors, for example, morphogenic proteins; a cytokine; an extracellular matrix molecule; an antimicrobial agent; an anti-inflammatory agent; and immunosuppressive agent, cel which support the therapeutic effect of the administered cells or combinations thereof. Incorporation of the biologically active agent into the microparticles of the cell / microparticle composition provides a sustained delivery of the biologically active agent at the treatment site. It is preferred that the biologically active agent enhances the primary therapeutic effect resulting from administration of the live cell / microparticle composition.
[0013]The composition and methods of the present invention provide a means for eliciting a therapeutic effect in a patient in need thereof by administering a composition comprising lives cells and a biocompatible, biodegradable polymer microparticle. Advantageously, the composition permits the administration to be by injection which obviates the need for an open surgical intervention to permit exposure of the treatment area and the disadvantages associated with open surgery (e.g., pain, infection, recovery time and cost). In addition, the microparticles of the composition can have incorporated therein a biologically active agent thereby providing at the treatement site a sustained release of an agent which can be complementary to or enhance the primary treatment.
[0014]Advantages of the cell / microparticle composition are also realized when the composition is used to generate tissue in vitro having a specific shape. That is, sintering offers advantages over known methods of shaped tissue formation since a greater number of cells can be initially loaded into the culture chamber of a specified shape, thereby providing the needed tissue in a shorter period of time.

Problems solved by technology

However, implantation of the scaffolds requires surgical intervention which presents disadvantages, such as the risk of infection and the need for invasive and painful procedures.
However, controlled delivery and containment of a liquid system within a particular area is difficult, and the liquid can spread to areas other than the implant site prior to solidification.

Method used

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  • Composition for the delivery of live cells and methods of use thereof
  • Composition for the delivery of live cells and methods of use thereof
  • Composition for the delivery of live cells and methods of use thereof

Examples

Experimental program
Comparison scheme
Effect test

example 1

Preparation of Microparticles

[0096]Microparticles were fabricated from PLG (50:50 lactide:glycolide, uncapped (—COOH), Mw˜10 kDa) using the General Process outlined above.

example 2

Cell Isolation-Chondrocytes

[0097]Bovine articular cartilage was harvested from the gelnohumeral and humeroulnar joints of neonatal calves and digested in 0.3% Type II collagenase at 37° C. for 12-16 hours overnight with shaking. Chondrocytes were passed through a 180 ÿm filter to remove large particulate material. Cells were washed 3 times with PBS and resuspended in complete medium (Ham's F12, 10% FBS, 0.3% carboxymethylcellulose, pen / strep / amphotericin B, and ascorbic acid).

example 3

Chondrocyte / Microparticle Adhesion Assay

[0098]Chondrocytes were mixed with 3.57 mg / mL of PLG (50:50 L:G) microparticles, prepared as described above, to a final concentration of 1×106 cells / mL. Control groups included cells alone and microparticles alone at the same concentrations as described above. The mixture of cells and microparticles contained phosphate buffered saline and cell culture medium.

[0099]The combined cell / microparticle suspension and controls were incubated on a shaker plate at 37° C. At 0, 2, 4, 16 hours, 1 mL samples were removed and assayed to determine the amount of cells which had adhered to the microparticles. In order to determine the amount of cells which had adhered to the microparticles, each sample was loaded onto a 3 mL histopaque density gradient and centrifuged for 5 min at 5000 rpm. The unattached cells were removed by decanting the less dense media fraction on top of the histopaque (approximately 1 mL). The remaining portion (approximately 3 mL) con...

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Abstract

The invention relates to an improved method for administering live cells to a patient and compositions useful in the method. The composition comprises live cells and biocompatible, biodegradable polymer microparticles. The cells and microparticles of the cell / microparticle composition can be contacted immediately prior to administration, or can be contacted in culture for a specified period of time prior to administration. In the method of the invention, an effective amount of the cell / microparticle composition is administered to a patient in need thereof by injection to a treatment site of the patient to provide a therapeutic effect in the patient. The therapeutic effect can be, for example, the formation of new tissue at the treatment site, or the production and secretion of a biologically active secretory molecule at the treatment site. The therapeutic effect resulting from injection of the cell / microparticle composition into a treatment site, is determined by the type of cell present in the composition. The composition comprising lives cells and biocompatible, biodegradable polymer microparticles can further comprise a biologically active agent. In a preferred embodiment, the biologically active agent is incorporated into the microparticle. The biologically active agent can be, for example, factors which modulate cell growth.

Description

RELATED APPLICATION(S)[0001]This application is a continuation of U.S. application Ser. No. 10 / 784,908, filed Feb. 23, 2004, which is a continuation of U.S. application Ser. No. 09 / 612,744, filed Jul. 10, 2000, now U.S. Pat. No. 6,719,970, issued Apr. 13, 2004. The entire teachings of the above application(s) are incorporated herein by reference.BACKGROUND OF THE INVENTION[0002]Implantable polymeric materials capable of being degraded and absorbed by the body have been used in medicine for many years. For example, implantable devices can be pre-seeded with a desired cell type, and used as structural supports or scaffolds for guiding tissue regeneration. One example is the regeneration of cartilage tissue using a degradable fiber mesh pre-seeded with chondrocytes as described in U.S. Pat. No. 5,041,138 to Vacanti et al. However, implantation of the scaffolds requires surgical intervention which presents disadvantages, such as the risk of infection and the need for invasive and painfu...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K35/12A61K9/14A61K35/32A61K35/39A61P3/10A61P19/04A61K35/30C12N5/077
CPCA61K35/32A61K35/30C12N2533/40C12N5/0655C12N2531/00A61K35/39A61P19/04A61P3/10
Inventor COSTANTINO, HENRY R.BONASSAR, LAWRENCE J.TRACY, MARK A.
Owner COSTANTINO HENRY R
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