Mul­ti­ply­ing stem cells

A re­searcher dis­cov­ers a tech­nique that might make it eas­ier and cheaper to re­place worn-out car­ti­lage.

The Star Malaysia - Star2 - - HEALTH - By TAN SHIOW CHIN

HAVE your knees started to creak? If your joints are be­gin­ning to make crack­ling noises when you bend them, this may be a sign that the car­ti­lage there is start­ing to wear out.

As car­ti­lage acts as a cush­ion to soften the im­pact of move­ments on our joints, this is not a good sign. Imag­ine your bones grind­ing to­gether ev­ery time you move – def­i­nitely a painful pro­posal!

Un­for­tu­nately, as we grow older, our car­ti­lage wears out through re­peated us­age. And that is the in­spi­ra­tion be­hind Univer­siti Malaya (UM) re­search sci­en­tist Chong Pan Pan’s cur­rent work.

“As we know, most peo­ple have knee prob­lems when they are older, that is os­teoarthri­tis. So I wanted to find some­thing to help solve their prob­lems,” she says.

The PhD stu­dent, who is at­tached to the Tis­sue En­gi­neer­ing Group in the Med­i­cal Fac­ulty’s Depart­ment of Orthopaedic Surgery, has come up with a method to in­crease the num­ber of mes­enchy­mal stem cells avail­able from a pa­tient’s blood.

New method

Mes­enchy­mal stem cells are a type of pluripo­tent stem cell that have the abil­ity to dif­fer­en­ti­ate into var­i­ous types of cells that make up our blood and con­nec­tive tis­sues (re­fer to Hi­er­ar­chy of stem cells). This in­cludes chon­dro­cytes, which are the cells that form car­ti­lage.

In adults, stem cells are usu­ally taken from the bone mar­row. How­ever, there is also a small amount of these cells float­ing around in our blood. The prob­lem is the num­ber of stem cells avail­able from blood is too small to be of prac­ti­cal use.

What Chong has dis­cov­ered is a method of sep­a­rat­ing the mes­enchy­mal stem cells from the rest of the blood, and grow­ing them in the lab­o­ra­tory.

Ac­cord­ing to her, this means that from a mere 2ml of blood, she can ob­tain around one mil­lion mes­enchy­mal stem cells, of which 90% can be dif­fer­en­ti­ated into chon­dro­cytes.

Al­though the num­ber of cells needed for car­ti­lage re­pair de­pends on the size of the de­fect, Chong es­ti­mates that a small de­fect would prob­a­bly re­quire around 10-20 mil­lion mes­enchy­mal stem cells.

“My ad­van­tage is that I can shorten the dif­fer­en­ti­a­tion time,” she says. “It usu­ally takes about three to four weeks, but I’ve man­aged to shorten it to two weeks.”

Cur­rently, the cell-based treat­ment pro­ce­dure for dam­aged knee car­ti­lage, known as an au­tol­o­gous chon­dro­cyte im­plan­ta­tion, re­quires two op­er­a­tions.

The first one is to al­low healthy car­ti­lage to be har­vested from the pa­tient’s knee us­ing an athro­scope. These cells are then cul­tured and grown in the lab­o­ra­tory un­til they reach the amount needed to cover the dam­aged area. This usu­ally takes around four to six weeks.

The sec­ond op­er­a­tion is to place these healthy cells onto the dam­aged area, where they are sup­pose to grow into new car­ti­lage.

But Chong says: “Au­tol­o­gous trans­plan­ta­tion works only if you still have car­ti­lage left (to trans­plant). If not, you have to do a to­tal knee re­place­ment.”

While us­ing mes­enchy­mal stem cells from bone mar­row also re­quires two sur­gi­cal pro­ce­dures – the first to har­vest the stem cells from the bone mar­row, and the sec­ond to place them on the dam­aged area – the ad­van­tage is that the har­vest­ing pro­ce­dure costs less and the knee only needs to un­dergo one pro­ce­dure.

Ac­cord­ing to Chong, 2ml of bone mar­row can pro­duce around three mil­lion mes­enchy­mal stem cells.

Al­though this is more than what even her new method of grow­ing stem cells from blood can pro­duce, the ad­van­tage in her method lies in the fact that the draw­ing of blood from pa­tients is a sim­ple and cheap pro­ce­dure.

It also means that pa­tients would only need to un­dergo one op­er­a­tion to place the new stem cells onto the dam­aged area.

A long way to go

But Chong cau­tions that her tech­nique is just mov­ing into the an­i­mal test­ing stage.

“To get to the pa­tient, there are three stages: the fun­da­men­tal re­search work, im­munoan­i­mal stud­ies, and the clin­i­cal tri­als.

“My col­leagues in the Tis­sue En­gi­neer­ing Group have just started the im­muno-an­i­mal test­ing,” she ex­plains.

She says that this stage will take one to two years as the re­searchers will have to take time to see if the blood-de­rived stem cells can re­pair car­ti­lage dam­age af­ter trans­plan­ta­tion, as well as to ob­serve if there are any side ef­fects from the pro­ce­dure.

“Clin­i­cal tri­als (in hu­man pa­tients) will also take an­other one to two years. So, the fastest we can in­tro­duce this to pa­tients would be within three to five years,” she says.

She adds that if the tri­als go well and re­ceives the ap­pro­pri­ate ap­proval, this treat­ment method will be of­fered at the UM Med­i­cal Cen­tre.

While Chong hopes that her tech­nique will help to phase out the need for to­tal knee re­place­ments in the fu­ture, she adds that only hos­pi­tals with lab­o­ra­tory fa­cil­i­ties will be able to pro­vide this method of treat­ment.

“Cell-based ther­apy like this needs lab fa­cil­i­ties, and you need to in­volve sci­en­tists to pre­pare the cells for cul­ture and growth,” she says.

In the mean­time, she is in the process of

Dr Chong Pan Pan found a way to sep­a­rate mes­enchy­mal stem cells from blood, and grow­ing them in the lab­o­ra­tory. patent­ing her tech­nique, as well as con­tin­u­ing her re­search work and PhD stud­ies.

Cur­rently, she is re­search­ing meth­ods to re­vert mes­enchy­mal stem cells back to pluripo­tent stem cells, so that a source of these cells – which can dif­fer­en­ti­ate into al­most any of the spe­cialised cells in our body – will be read­ily avail­able in our own bod­ies for fu­ture ther­a­peu­tic use.

Im­por­tant dis­cov­ery:

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