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Autologous Bone Marrow Stem Cell Therapy for Ischemic Ulcer of Lower Limb in a Diabetic Patient.
Subrammaniyan SR(1), Amalorpavanathan J(1), Shankar(1), Rajkumar(1), Farzana BL(1), Manjunath S(1), Senthilkumar R(1), Mohanashankar M(1), Sheriff AK(1), Naveen AT(1), Abraham S(1,3).
- Vascular Surgery Dept., Vijaya Hospital Chennai, India.
- Nichi-In centre for Regenerative Medicine, Chennai, India.
- Yamanashi University- School of Medicine, Tamaho, Japan.
Background: Chronic limb ischemia is an outcome of peripheral arterial occlusive disease. If
revascularization cannot be done, amputation is the only option left. Recent studies report that the
injection of bone marrow mononuclear cells or Peripheral blood mononuclear cells rich in CD34+
cell content have resulted in Neoangiogenesis and have improved the functional activity of the
ischemic limb and regression of the injuries and infection witnessed due to the ischemic limb and
healing of ulcer. Here we report our experience with one such case.
Materials and Methods: A 68-year-old female with critical limb ischemia with an ulcer in the
left leg measuring 30X12 cm over the posterior portion of the leg and extending to the medial
aspect of the foot measuring 14X10 cm. A lateral extension of the wound was present in two
places each measuring 4.5X4.0 cm. She was treated by Autologous Bone marrow stem cells
injection in two sittings at an interval of one month. Under short general anesthesia, 110 ml of
Bone marrow was aspirated each time, transported in Acid Citrate Dextrose and was processed
for mononuclear cells (MNC) by ficoll density gradient centrifugation, following the cGMP
protocol. The MNC concentrate was injected at various sites in the Gastrocnemius muscle and the
surrounding area after necessary debridement. First injection of MNC contained 603 Million cells
and the second, 786 Million cells. The patient was followed up at regular intervals after the
injections. Skin grafting was performed to the uncovered areas of the wound on the 57th day from
the first injection and from the 75th day, she could walk by herself.
Results: The healthy granulation gradually started appearing in the areas which were previously
unhealthy and ischemic. Skin started growing from the edges of the wound and fully covered the
lateral two wounds and 23% of the foot area of the wound. Approximately 15% of the wound
surface of the posterior of the leg was covered with the in-growing skin at the time of skin
grafting. Angiogram revealed new collaterals and also a patent Posterior tibial artery through
collateral supply which was previously found occluded. The Ankle-Brachial Index improvement
was also significant. Three months after the treatment, she is free from symptoms of claudication
or foot-drop.
Conclusion: Autologous Bone Marrow derived stem cell therapy has been used for treatment of
CLI in many parts of the world, but not in such a large wound of the size, that too in a diabetic
patient as reported in this study. As Autologous Bone Marrow stem cell therapy helps in
neoangiogenesis and wound healing process in case of chronic ischemic wounds it can be applied
in cases as reported herewith. 
Autologous Bone Marrow Stem Cell Therapy for an Ischemic U1cer of Lower Limb in a Diabetic Patient.
Subrammaniyan SR(I), Rajkumar M(I),Amalorpavanathan J(I) Shankar R(I), Farzana L(2),
Manjunath S(2), Senthil RS(2), Sheriff AK(2), Dominic J (2), Abraham S(2,3).
- Dept.of Vascular Surgery, Vijaya Hospital Chennai, India.
- Nichi-In centre for Regenerative Medicine, Chennai, India.
- Yamanashi University, Tamaho ,Japan.
Background: Chronic limb ischemia is an outcome of peripheral arterial disease. If revascularization cannot be done, amputation is the only option left. Recent studies report that the injection of Bone marrow mononuclear cell concentrate with stem cells or Peripheral blood mononuclear cells rich in CD34+ cell content have resulted in angiogenesis, improved the functional activity of the ischemic limb and enhanced the healing of the ischemic ulcer. Here we report our experience with one such case.
Materials and Methods: A 68-year-old diabetic female patient with critical limb ischemia of the left lower limb with diffuse multiple critical stenosis of the only patent Tibial artery with a large ischemic ulcer with infection. The ulcer measured 30X12 cm at the posterior of the calf, exposing the Gastrocnemius and Achilles tendon and extending to the medial aspect of the foot measuring 14 X 10cm. A lateral extension of the wound was present as two places just above the ankle joint, each measuring 4.5 X 4.0 CM. The patient had been advised amputation of the lower limb elsewhere. She was administered Autologous Bone Marrow Stem Cell Therapy (ABMSCT) twice at an interval of one month. 110 ml of Bone marrow was aspirated each time under short general anesthesia, transported in Acid Dextrose Citrate and was processed for mononuclear cells (MNC) by ficoll density gradient centrifugation, as per cGMP Protocol. The MNC concentrate was injected at various sites in the Gastrocnemius muscle and the surrounding area after necessary wound debridement. First time the MNC concentration injected, contained 603 Million cells and the second time 786 Million cells. The patient was followed up regularly for all relevant parameters. Skin grafting was performed to the uncovered areas of the wound on the 57th day from the first stem cell injection. Angiography was done to adjudge the progress.
Results: The healthy granulation gradually started appearing in the areas which were initially unhealthy and ischemic. Skin started growing from the edges of the wound and fully covered the lateral two wounds and 23% of the area of the wound on the medial side of the foot. Approximately 15% of the wound surface of the posterior of the calf was covered with the in growing skin at the time of skin grafting.
Conclusion: ABMSCT has been reported for treatment of CLI in many parts of the world, but not in such a large wound of the size that we have come across. As ABMSCT enhances the wound healing process in case of chronic ischemic wounds we recommend that it may be considered in cases similar to what we have experienced, before deciding on an amputation, to salvage the limb
Ischemic Ulcer of a Lower Limb in a Diabetic patient, treated with autologous bone marrow stem cells- A case Report.
Abraham S(1), Amalorpavanathan (2), Rajkumar M(2), Shankar R(2), Farzana BL (3), Manjunath S (3), Senthilkumar R(3), Mohanashankar M(3), Sheriff AK(3), Naveen AT(3), Subrammaniyan SR (2).
- Yamanashi University School of Medicine, Kofu shi ,Japan.
- Vascular Surgery, Vijaya Hospital Chennai, India.
- Nichi-In centre for Regenerative Medicine, Chennai, India.
Background: Chronic limb ischemia is an outcome of peripheral arterial
occlusive disease. When conventional medical and surgical treatments are
not feasible, amputation is the only option left. Recent studies report that
the injection of bone marrow mononuclear cells and Peripheral blood
mononuclear cells rich in C034+ cells have resulted in symptomatic recovery,
improved functional activity of the ischemic limb as well as healing of the
ulcers. Here we report our experience with one such case where autologous
bone marrow mononuclear cells were injected and the patient followed up
for 6 months.
Materials and Methods: A 68-year-old female with critical limb
ischemia with an ulcer in the left leg measuring 30X 12 cm over the posterior
portion of the leg and extending to the medial aspect of the foot measuring
14X10 cm. A lateral extension of the wound was present in two places each
measuring 4.5X4.0 cm. She was treated by Autologous Bone marrow stem
cells injection in two sittings at an interval of one month. Under short general
anesthesia, 110 ml of Bone marrow was aspirated each time, transported
in Acid Citrate Dextrose and was processed for mononuclear cells (MNC) by
Ficoll density gradient centrifugation, following the cGMP protocols. The
MNC concentrate was injected at various sites in the Gastrocnemius muscle
and the surrounding area after necessary debridement. First injection of
MNC contained 603 Million cells and the second, 786 Million cells. Skin grafting was performed to the uncovered areas of the wound on the 57th
day from the first injedion. The patient has been followed up at regular
intervals for six months after the treatment with investigations such as
Ankle-Brachial Index, Doppler and Angiogram.
Results: The healthy granulation
gradually started appearing in the areas which were previously
unhealthy and ischemic Skin started growing from the edges of the wound
and fully covered the lateral two wounds and 23% of the foot area of the
wound. Approximately 15% of the wound surface of the posterior of the leg
was covered with the in-growing skin at the time of skin grafting.
Angiogram revealed new collaterals and also a patent Posterior tibial artery
through collateral supply which was previously found occluded. The Ankle-
Brachial Index improvement was also significant Six months after the treatment,
she is free from symptoms of claudication or foot-drop.
Conclusion:
Autologous Bone Marrow derived stem cell therapy has been used for treatment
of CLI in many parts of the world, but not in such a large wound of
the size, that too in a diabetic patient as reported in this study. As
Autologous Bone Marrow stem cell therapy helps in neoangiogenesis and
wound healing process in case of chronic ischemic wounds it can be applied
in cases as reported herewith.
Our Experience in treating Ischemic Ulcer of a Lower Limb in 4 diabetic patients with Autologous Bone Marrow Stem Cells.
Subrammaniyan S R(1), Rajkumar M(1), Amalorpavanathan J(1), Shankar R(1), Manjunath S(2), Senthil Kumar R(2), Abraham S(2,3).
- Dept.of Vascular Surgery, Vijaya Hospital Chennai, India
- Nichi-In centre for Regenerative Medicine, Chennai, India.
- Yamanashi University, Tamaho ,Japan
Background: Chronic limb ischemia is an outcome of peripheral arterial occlusive disease. When conventional medical and surgical treatments are not feasible, amputation is the only option left. Recent studies report that the injection of bone marrow mononuclear cells and Peripheral blood mononuclear cells rich in CD34+ cells have resulted in symptomatic recovery, improved functional activity of the ischemic limb as well as healing of the ulcers. Here we report our experience with 4 patients of such case where autologous bone marrow mononuclear cells were injected and the patient followed up for 6 months. Materials and Methods: Four patients with critical limb ischemia with ulcers were referred for amputation of their limb. A 68-year-old female with critical limb ischemia with an ulcer in the left leg measuring 30X12 cm over the posterior portion of the leg and extending to the medial aspect of the foot measuring 14X10 cm, a 65-year-old male with necrotic wound in his lower foot, a 69-year-old male with a deep wound in his lower foot and a 61-year-old male with ulcer in his toe amputated with all the toe fingers. The first two patients were given injections for more than one sitting at appropriate intervals specified by the clinician. Under short general anesthesia, 110 ml of Bone marrow was aspirated each time, transported in Acid Citrate Dextrose and was processed for mononuclear cells (MNC) by Ficoll density gradient centrifugation, following the cGMP protocols. The MNC concentrate was injected at various sites in the Gastrocnemius muscle and the surrounding area after necessary debridement. Skin grafting was performed in the first two patients and followed up for a period of at regular intervals of 6 to 9 months. The patients have been followed up at regular intervals for six months after the treatment with investigations such as Ankle-Brachial Index, Doppler and Angiogram.
Results: All the patients showed improvements with healthy granulation gradually started appearing in the areas which were previously unhealthy and ischemic. Slow granulation was found in-patient 3 and but the patient 4 died because of other factor such as renal failure, peritoneal dialysis and cardiac failure. Patients 1 and 2 had healthy granulation, uniform revascularization and after a period of 9 months, healing was completely possible.
Conclusion: Stem cell therapy is definitely useful where, revascularization is not feasible at the same time, renal failure, cardiac failure, etc do present some difficulties. All the parameters need to be taken care. Growth factors or plastic surgery need not be used for stem cell therapy thus considering only the appropriate time of injections. As Autologous Bone Marrow stem cell therapy helps in neoangiogenesis and wound healing process in case of chronic ischemic wounds it can be applied in cases as reported herewith.
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