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"This updatable book provides an accessible informative overview of the current state of the art in nerve repair research.The introduction includes history of nerve repair research and establishes key concepts and terminology and will be followed by sections that represent the main areas of interest in the field: (1) Biomaterials, (2) Therapeutic Cells, (3) Drug, Gene and Extracellular Vesicle Therapies, (4) Research Models and (5) Clinical Translation. Each section will contain 3 - 6 chapters, capturing the full breadth of relevant technology. Bringing together diverse disciplines under one overarching theme echoes the multidisciplinary approach that underpins modern tissue engineering and regenerative medicine. Each chapter will be written in an accessible manner that will facilitate interest and understanding, providing a comprehensive single reference source. The updatable nature of the work will ensure that it can evolve to accommodate future changes and new technologies. The main readership for this work will be researchers and clinicians based in academic, industrial and healthcare settings all over the world."

"Cedera saraf tepi merupakan salah satu penyebab disabilitas di dunia. Cedera saraf tepi akan merangsang badan neuron motorik untuk mengalami kromatolisis. PRP saat ini dianggap bermanfaat untuk regenerasi sel saraf karena mengandung berbagai faktor pertumbuhan yang berperan dalam neuron survival dan pertumbuhan akson. Penelitian ini bertujuan untuk mengetahui peran PRP terhadap fungsi berjalan melalui regerasi neuron motorik di medulla spinalis. Penelitian menggunakan enam kelompok tikus wistar jantan yang diberi perlakuan operasi sham, model skiatika, dan model skiatika yang diberi PRP. Tikus dilakukan terminasi pada hari ke-7 dan 42. Model skiatika dibuat dengan melakukan penjepitan di nervus ischiadicus selama 3 menit. Pemeriksaan histologi menggunakan pewarnaan hematoksilin eosin dan toluidine blue pada sediaan medulla spinalis tikus untuk menilai densitas badan nissl. Ekspresi marker regenerasi menggunakan pemeriksaan imunohistokimia GAP-43. Fungsi motorik dinilai setiap minggu menggunakan Sciatic Functional Index (SFI) dan Foot Fault Test (FFT). Terdapat perbedaan signifikan pada pemeriksaan densitas badan nissl neuron motorik di medulla spinalis pada hari ke-42. Pemeriksaan motorik dengan pengukuran SFI dan FFT menunjukkan perbedaan signifikan pada hari ke-7 dan 14. Hasil penelitian menunjukkan bahwa pemberian terapi PRP dapat mempercepat regenerasi saraf perifer yang ditandai dengan peningkatan badan nissl dan perbaikan fungsi motorik.

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Peripheral nerve injury is one of the leading causes of disability. Peripheral nerve injury stimulates motor neuron bodies to undergo chromatolysis. PRP is currently considered beneficial for nerve cell regeneration. It contains growth factors that affect neuron survival and axon growth. This study aims to determine PRP’s role on walking function through motor neuron regeneration in spinal cord. The study used six groups of male wistar rats treated with sham surgery; sciatica model; sciatica+PRP. The rats were terminated on days 7 and 42. Sciatica model was made by clamping the sciatic nerve for 3 minutes. Histological examination using hematoxylin eosin and toluidine blue staining on rat spinal cord to assess Nissl body density. Expression of regeneration markers using GAP-43 immunohistochemistry. Motor function was assessed weekly with Sciatic Functional Index (SFI) and Foot Fault Test (FFT). There was a significant difference in the examination of the density of the nissl body of motor neurons on day 42. Motor examination with SFI and FFT measurements showed significant differences on the 7th and 14th days. The results showed that PRP therapy could accelerate peripheral nerve regeneration which was characterized by an increase in nissl body and motor function improvement."

"Latar belakang: Cidera saraf perifer sebagai keluaran dari post operatif hingga saat ini belum ditangani dengan maksimal. Penelitian ini ditujukan untuk menentukan potensi dari sekretom pada regenerasi cidera saraf perifer.Metode: Cidera saraf perifer buatan dilakukan pada tikus dengan melakukan diseksi pada saraf sciatic. Evaluasi perbaikan motorik dilakukan mengunakan Sciatic Functional Index (SFI) pada minggu ke enam (SFI 1), minggu ke sembilan (SFI 2), dan minggu ke dua belas (SFI 3). Rasio berat basah antara otot gastrocnemius kanan dan kiri dibandingkan serta dilakukan histomorphometry saraf sciatic pada tiap kelompok.Hasil: Kelompok III menunjukan SFI 1 yang lebih baik dibandingkan kelompok I (p=0.017). Kelompok I dan III menunjukan perbedaan SF2 yang signifikan dibandingkan dengan kelompok II dan IV (p<0.001). Rasio tertinggi dari otot gastrocnemius ditemukan pada kelompok I dan III, yang bernilai 0.65 ± 0.059 dan 0.67 ± 0.179 (p<0.001). Pada histomorphometry, akson termyelinisasi paling banyak ditemukan pada kelompok I dan III, yang bernilai p<0.001.Kesimpulan: Sekretom sel punca mesenkimal korda umbilikalis dapat digunakan sebagai terapi baru untuk menggantikan autograf pada penanganan kerusakan saraf perifer.

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Background: Currently, the post-surgical outcome of peripheral nerve injury has not been optimal. The purpose of this research is to determine the potency of secretome in peripheral nerve injury regeneration.

Method: The mice had artificially-induced peripheral nerve injury, which was created by dissecting the sciatic nerve. Sciatic Functional Index (SFI) was used to evaluate the motoric recovery on week six (SFI 1), week nine (SFI 2), and week twelve (SFI 3). The mice was sacrificed on week twelve. The wet mass ratios of the right and left gastrocnemius muscle were compared, then the sciatic nerve histomorphometry evaluation was performed on each group.

Results: Group III showed a better SFI 1 result than Group I (p=0.017). Group I and III showed significantly better SFI 2 than group II and IV (p<0.001). The highest ratio of gastrocnemius muscle was found in group I and III, which were 0.65 ± 0.059 and 0.67 ± 0.179 (p<0.001). On histomorphometry, the highest number of myelinated axons were found in group I and III, which were p<0.001.

Conclusion: Umbilical cord mesenchymal stem cell secretome can be used as a new therapy to replace the autograft in peripheral nerve defect management."

"ABSTRAKGangguan saraf fasialis prefer unilateral merupakan suatu gangguan pada saraf fasialis akibat kelumpuhan otot sebagian atau seluruh wajah. Dalam menangani kasus saraf fasialis perifer unilateral, setiap klinisi dapat menggunakan beberapa modalitas pemeriksaan seperti pemeriksaan motorik sistem Freyss, House-Brackmann, uji topognostik (schirmer, refleks stapedius, gustatometri) dan pemeriksaan elektrofisiologis (kecepatan hantaran saraf, refleks blink, jarum EMG) dalam menentukan derajat kerusakan saraf dan letak lesi berdasarkan onset, derajat kerusakan saraf dan etiologi dalam membantu menegakkan diagnosis dan memperkirakan prognosis. Sangat penting dalam menyampaikan informasi yang tepat dan efektif antar klinisi mengenai keadaan saraf fasialis yang mengalami paresis saraf fasialis dalam menentukan tatalaksana selanjutnya. Penelitian ini menggunakan metode deskriptif cross-sectional dengan pengambilan subjek penelitian secara consecutive sampling di poliklinik Neurotologi THT dan poliklinik EMG Neurologi RSUPN dr. Cipto Mangunkusumo pada bulan Agustus 2012 sampai dengan Mei 2013 dan didapatkan sebanyak 44 subjek penelitian.Berdasarkan hasil penelitian ini didapatkan hubungan yang bermakna dan kesesuaian yang cukup (Kappa R =0,5, p<0,05) pada 32 subjek penelitian dengan onset lama dengan derajat kerusakan sedang dan berat antara pemeriksaan motorik sistem Freyss, House-Brackmann dengan pemeriksaan elektrofisiologis. Pada penelitian ini tidak didapatkan hubungan yang bermakna dan kesesuaian yang baik (Kappa R=0,011, p=0,935) dalam menentukan letak lesi antara pemeriksaan uji topognostik dengan pemeriksaan elektrofisiologis. Tiga belas subjek penelitian tidak dapat ditentukan letak lesi berdasarkan pemeriksaan elektrofisiologis pada onset kronis dengan derajat kerusakan sedang dan berat sedangkan pemeriksaan uji topognostik mampu menentukan letak lesi pada onset akut maupun kronis. Untuk daerah-daerah yang tidak memiliki modalitas pemeriksaan elektrofisiologis, pemeriksaan motorik sistem Freyss dan House-Brackmann dapat digunakan dalam menegakkan diagnosis dan memprediksi prognosis.

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ABSTRACTUnilateral peripheral facial nerve palsy is a disturbance in facial nerve caused by partial or complete muscle paralysis. Clinician can use multiple examination modality such as Freyss system, House-Brackmann, topognostic test (schirmer, stapedius reflex, gustatometry) and electrophysiology (nerve conduction velocity, blink reflex, EMG needle) to establish diagnosis and prognosis. It is very important to deliver right and effective information between clinician about facial nerve condition and paralysis to determine further management. Achieve conformity between Freyss system, House-Brackmann, topognostic study and electophysiologic examination in diagnosis and prognosis. This study used descriptive cross-sectional method by taking study subject with consecutive sampling in Neurotology division of ENT department and EMG division of Neurology Department outpatient-clinic and 44 study subjects.According to study result, there is significance and conformity (Kappa R =0,5, p=0,005) for 32 subjects late onset with detriment degree moderate severe between motoric examination Freyss, House-Brackmann and electrophysiologic examination. In this study there is no significanceand conformity (Kappa R=0,011, p=0,935) between determining lesion site between topognostic test and electrophysiology examination. Thirteen study subjects could not be determined for lesion site, due to chronic onset with moderate severe damage by electrophysiology examination, whereas topognostic test can determine lesion site in acute nor chronic onset. In region without facility for electrophysiologic examination, Freyss and House-Brackmann motoric system can be used in establishing diagnosis and determining prognosis."

"Cedera saraf perifer merupakan beban klinis yang besar. Berbagai modalitas terapi dikembangkan untuk mencapai perbaikan fungsi, salah satunya dengan platelet-rich plasma (PRP). Walaupun PRP sudah diterapkan secara klinis, namun proses intrinsik di dalamnya belum sepenuhnya diketahui. Oleh karena itulah penelitian ini dibuat untuk mengetahui efek pemberian PRP terhadap populasi sel Schwann dan makrofag pada lokasi cedera saraf perifer. Penelitian eksperimental dengan sampel tikus Wistar, terdiri dari tiga kelompok penelitian untuk masing-masing terminasi di hari ke-3 dan hari ke-7, yaitu kontrol, model sciatica, dan model sciatica yang diberi PRP. Model sciatica dilakukan dengan metode crush injury. Fungsi motorik dinilai pada hari ke-3 dan ke-7 menggunakan Sciatic Functional Index (SFI) dan Foot Fault Test (FFT). Ekspresi marker sel Scwann diperiksa dengan imunohistokimia (IHK) SOX10, dan ekspresi marker sel makrofag dengan IHK CD68. Fungsi motorik meningkat pada hari ke-7 (p<0,05), dan populasi sel Schwann meningkat pada hari ke-7 (p<0,05). Pemberian PRP mempengaruhi proses regenerasi saraf perifer model tikus sciatica.

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Peripheral nerve injury is a large clinical burden. Various therapeutic modalities have been developed to achieve improved function, one of which is with platelet-rich plasma (PRP). Although PRP has been applied clinically, the intrinsic processes are not fully understood. For this reason, this study was made to determine the effect of PRP administration on the Schwann cell population and macrophages at the site of peripheral nerve injury. Experimental study with samples of Wistar rats, consisted of three research groups for termination on day 3 and day 7 respectively, namely control, sciatica model, and sciatica model treated with PRP. The sciatica model was performed using the crush injury method. Motor function was assessed on day 3 and 7 using the Sciatic Functional Index (SFI) and Foot Fault Test (FFT). Schwann cell marker expression was examined by SOX10 immunohistochemistry (IHC), and macrophage cell marker expression was examined by CD68 IHC. Motor function increased on day 7 (p<0.05), and the Schwann cell population increased on day 7 (p<0.05). PRP administration affects the process of peripheral nerve regeneration in the sciatica rat model."

"[ABSTRAKLatar belakang: Malignant peripheral nerve sheath tumor (MPNST) adalah sarkoma jaringan lunak yang sulit dibedakan dengan beberapa sarkoma sel spindel karena morfologinya yang serupa. MPNST bersifat agresif dengan angka rekurensi yang tinggi dan cenderung bermetastasis terutama ke paru. Salah satu tahap metastasis adalah invasi dengan cara mendegradasi matriks ekstraseluler dimana Matrix Metalloproteinase (MMP) memainkan peranan penting dalam proses ini. MMP tipe gelatinase yaitu MMP-2 dan MMP-9 memiliki kemampuan dalam mendegradasi membran basal dan kolagen fibrilar sehingga dapat membuka jalur invasi bagi sel tumor. MMP-2 mampu mendegradasi lebih banyak tipe kolagen dan MES non kolagen dibandingkan MMP-9. Penelitian ini bertujuan untuk menilai hubungan antara peningkatan ekspresi MMP-2 dengan derajat keganasan histologik dan variabel prognostik klinis lainnya.Bahan dan cara: Dilakukan pulasan imunohistokimia MMP-2 pada 39 kasus yang terdiri atas 19 MPNST derajat rendah dan 20 MPNST derajat tinggi. Selanjutnya dilakukan analisis hubungan antara peningkatan ekspresi MMP-2 dengan derajat keganasan dan variabel klinis seperti usia, jenis kelamin, ukuran dan lokasi tumor.Hasil: Peningkatan ekspresi MMP-2 ditemukan pada 19 (95%) kasus MPNST derajat tinggi dan 3 kasus (15,8%) kasus MPNST derajat rendah (p=0.000). Terdapat hubungan yang kuat antara peningkatan ekspresi MMP-2 dengan derajat keganasan MPNST. Tidak ditemukan hubungan antara ekspresi MMP-2 dengan jeni usia, jenis kelamin, ukuran dan lokasi tumor.Kesimpulan: Peningkatan ekspresi MMP-2 sejalan dengan peningkatan derajat histologik, sehingga dapat digunakan untuk membantu menentukan progresifitas MPNST.

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ABSTRACTBackground: Malignant peripheral nerve sheath tumor (MPNST) is a sarcoma that is difficult to differentiate with other spindle cell sarcomas, because of their similar morphology. The behavior of MPNST is aggressive, with a high recurrence and tend to metastases hematogenous, especially to lung. Important step of metastases is invasion by degradating extracellular matrix, in which Matrix Metalloproteinase (MMP) play important role in this process. Gelatinase type of MMP, MMP-2 and MMP-9 have ability to degrade basal membrane and fibriler collagen, in order to open the way of invasion. MMP-2 can degrade type collagen and non collagen extracellular matrix than MMP-9. The aim of this study is to see the correlation between expression of MMP-2 and histopathology grading and other prognostic clinical variables.Methods: This study enrolled 39 cases of consisted of 19 low grade MPNST and 20 high grade MPNST. The case were stained for MMP-2 imunnohistochemistry and the expression of MMP-2 were scored. Analysis the correlation between over expression of MMP-2 and histopathology grading and other clinical variables , such as age, sex, size and location of the tumor.Results: Overexpression of MMP-2 was observed in 19 (95%) cases of high grade MPNST and 3 (15,8%) cases of low grade MPNST (p=0.000). There is a significant correlation between MMP-2 over expression and histopathology grade. There is no correlation between MMP-2 expression and age, sex, siize and location of tumor.Conclusion: High expression of MMP-2 is in parallel with high histologic grade, therefore it may be of additional use as prognostic factor., ackground: Malignant peripheral nerve sheath tumor (MPNST) is a sarcoma that is difficult to differentiate with other spindle cell sarcomas, because of their similar morphology. The behavior of MPNST is aggressive, with a high recurrence and tend to metastases hematogenous, especially to lung. Important step of metastases is invasion by degradating extracellular matrix, in which Matrix Metalloproteinase (MMP) play important role in this process. Gelatinase type of MMP, MMP-2 and MMP-9 have ability to degrade basal membrane and fibriler collagen, in order to open the way of invasion. MMP-2 can degrade type collagen and non collagen extracellular matrix than MMP-9. The aim of this study is to see the correlation between expression of MMP-2 and histopathology grading and other prognostic clinical variablesMethods: This study enrolled 39 cases of consisted of 19 low grade MPNST and 20 high grade MPNST. The case were stained for MMP-2 imunnohistochemistry and the expression of MMP-2 were scored. Analysis the correlation between over expression of MMP-2 and histopathology grading and other clinical variables , such as age, sex, size and location of the tumor.Results:. Overexpression of MMP-2 was observed in 19 (95%) cases of high grade MPNST and 3 (15,8%) cases of low grade MPNST (p=0.000). There is a significant correlation between MMP-2 over expression and histopathology grade. There is no correlation between MMP-2 expression and age, sex, siize and location of tumor.Conclusion: High expression of MMP-2 is in parallel with high histologic grade, therefore it may be of additional use as prognostic factor.]"

"This volume presents a new contribution for the field of Tissue Engineering with a focus on the development of mathematical and computational methods that are relevant to understand human tissues, as well to model, design, and fabricate optimized and smart scaffolds."

"Pendahuluan: Cedera saraf tepi dapat menyebabkan cacat fungsional yang parah. Denervasi yang berkepanjangan menyebabkan perubahan permanen pada organ target sekalipun dilakukan operasi dengan teknik rekonstruksi saraf bedah mikro. Oleh karena itu, banyak penelitian regeneratif telah dilakukan untuk meningkatkan luaran fungsional setelah tindakan rekonstruksi saraf pada cedera saraf tepi.Metode: Dilakukan transeksi komplet saraf iskiadikus tungkai belakang kanan pada 20 tikus Sprague-Dawley jantan. Setiap ujung saraf dijahit ke otot terdekat untuk mencegah pertumbuhan saraf spontan. Setelah 3 minggu denervasi, dilakukan penyambungan saraf dan implantasi sel punca mesenkimal (SPM) ke neuromuscular junction (NMJ) otot gastroknemius pada kelompok perlakuan (n=10). Sepuluh tikus lainnya (kelompok kontrol) menerima plasebo (NaCL). Delapan minggu setelah penyambungan saraf, seluruh sampel dinilai luaran fungsional dengan analisis walking track dan studi neurofisiologi yang dilakukan sebelum terminasi. Berat otot basah dievaluasi kemudian dilakukan pemeriksaan histomorfometri.Hasil dan Diskusi: Denervasi saraf iskiadikus selama tiga minggu menghasilkan model cedera saraf perifer kronis yang secara klinis mengakibatkan gangguan berjalan dan secara histologis menyebabkan degenerasi otot gastroknemius. Tidak ada perbedaan analisis walking track, compound muscle action potential (CMAP) dan berat otot basah antara kedua kelompok. Namun, penyambungan saraf yang dikombinasikan dengan implantasi SPM memberikan gambaran preservasi NMJ dan regenerasi otot yang lebih baik sebagai organ target saraf yang terbukti secara histologis dengan fragmentasi reseptor asetilkolin (AChR) yang jauh lebih rendah, jumlah dan kepadatan AChR yang lebih besar, serta diameter serat otot yang lebih besar.Kesimpulan: Implantasi SPM di NMJ berpotensi menunda degenerasi organ target dan meningkatkan regenerasi

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Introduction: Peripheral nerve injury is a devastating condition that can lead to severe functional disabilities. Despite the use of advanced microsurgical nerve reconstruction techniques, prolonged denervation causes irreversible changes in target organs. Thus, many regenerative studies have been conducted to increase functional outcomes in animal models.

Methods: Complete sciatic nerve transection was performed on the right hind limb of 20 male Sprague-Dawley rats. Each nerve end was sutured to the approximate muscle at a distance to prevent spontaneous nerve regrowth. After 3 weeks of denervation, the nerve was repaired and mesenchymal stem cells was injected directly to the gastrocnemius neuromuscular junction (NMJ) in MSCs group (n=10) and the rest of the rats (control group) received placebo (normal saline). Clinically, all sample were observed by walking track analysis and a neurophysiology study which was done before termination (8 weeks after nerve repair). Postmortem wet muscle weight was evaluated, and histological examination was performed

Result and Discussion: Three weeks sciatic nerve denervation produce the chronic peripheral nerve injury model which resulted clinically as gait disturbance and histologically as gastrocnemius muscle degeneration. There was no difference in walking track analysis, compound muscle action potential (CMAP) and muscle weight between two groups. However, the delayed nerve repair combined with stem cell implantation gives a better NMJ and muscle regeneration as the nerve target organ that proven histologically with a significantly lesser acetylcoline receptor (AChR) fragmentation, greater AChR amount and density, as well as larger muscle fiber diameter.

Conclusion: Mesenchymal stem cell direct implantation in neuromuscular junction possibly delayed the end organ degeneration and enhanced regeneration proven by a better morphometry profile in MSCs group."

"Pendahuluan: Cedera saraf tepi dapat menyebabkan cacat fungsional yang parah. Denervasi yang berkepanjangan menyebabkan perubahan permanen pada organ target sekalipun dilakukan operasi dengan teknik rekonstruksi saraf bedah mikro. Oleh karena itu, banyak penelitian regeneratif telah dilakukan untuk meningkatkan luaran fungsional setelah tindakan rekonstruksi saraf pada cedera saraf tepi.Metode: Dilakukan transeksi komplet saraf iskiadikus tungkai belakang kanan pada 20 tikus Sprague-Dawley jantan. Setiap ujung saraf dijahit ke otot terdekat untuk mencegah pertumbuhan saraf spontan. Setelah 3 minggu denervasi, dilakukan penyambungan saraf dan implantasi sel punca mesenkimal (SPM) ke neuromuscular junction (NMJ) otot gastroknemius pada kelompok perlakuan (n=10). Sepuluh tikus lainnya (kelompok kontrol) menerima plasebo (NaCL). Delapan minggu setelah penyambungan saraf, seluruh sampel dinilai luaran fungsional dengan analisis walking track dan studi neurofisiologi yang dilakukan sebelum terminasi. Berat otot basah dievaluasi kemudian dilakukan pemeriksaan histomorfometri.Hasil dan Diskusi: Denervasi saraf iskiadikus selama tiga minggu menghasilkan model cedera saraf perifer kronis yang secara klinis mengakibatkan gangguan berjalan dan secara histologis menyebabkan degenerasi otot gastroknemius. Tidak ada perbedaan analisis walking track, compound muscle action potential (CMAP) dan berat otot basah antara kedua kelompok. Namun, penyambungan saraf yang dikombinasikan dengan implantasi SPM memberikan gambaran preservasi NMJ dan regenerasi otot yang lebih baik sebagai organ target saraf yang terbukti secara histologis dengan fragmentasi reseptor asetilkolin (AChR) yang jauh lebih rendah, jumlah dan kepadatan AChR yang lebih besar, serta diameter serat otot yang lebih besar.Kesimpulan: Implantasi SPM di NMJ berpotensi menunda degenerasi organ target dan meningkatkan regenerasi

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Introduction: Peripheral nerve injury is a devastating condition that can lead to severe functional disabilities. Despite the use of advanced microsurgical nerve reconstruction techniques, prolonged denervation causes irreversible changes in target organs. Thus, many regenerative studies have been conducted to increase functional outcomes in animal models.

Methods: Complete sciatic nerve transection was performed on the right hind limb of 20 male Sprague-Dawley rats. Each nerve end was sutured to the approximate muscle at a distance to prevent spontaneous nerve regrowth. After 3 weeks of denervation, the nerve was repaired and mesenchymal stem cells was injected directly to the gastrocnemius neuromuscular junction (NMJ) in MSCs group (n=10) and the rest of the rats (control group) received placebo (normal saline). Clinically, all sample were observed by walking track analysis and a neurophysiology study which was done before termination (8 weeks after nerve repair). Postmortem wet muscle weight was evaluated, and histological examination was performed

Result and Discussion: Three weeks sciatic nerve denervation produce the chronic peripheral nerve injury model which resulted clinically as gait disturbance and histologically as gastrocnemius muscle degeneration. There was no difference in walking track analysis, compound muscle action potential (CMAP) and muscle weight between two groups. However, the delayed nerve repair combined with stem cell implantation gives a better NMJ and muscle regeneration as the nerve target organ that proven histologically with a significantly lesser acetylcoline receptor (AChR) fragmentation, greater AChR amount and density, as well as larger muscle fiber diameter.

Conclusion: Mesenchymal stem cell direct implantation in neuromuscular junction possibly delayed the end organ degeneration and enhanced regeneration proven by a better morphometry profile in MSCs group."

"This reference work presents the origins of cells for tissue engineering and regeneration, including primary cells, tissue-specific stem cells, pluripotent stem cells and trans-differentiated or reprogrammed cells. There is particular emphasis on current understanding of tissue regeneration based on embryology and evolution studies, including mechanisms of amphibian regeneration. The book covers the use of autologous versus allogeneic cell sources, as well as various procedures used for cell isolation and cell pre-conditioning , such as cell sorting, biochemical and biophysical pre-conditioning, transfection and aggregation. It also presents cell modulation using growth factors, molecular factors, epigenetic approaches, changes in biophysical environment, cellular co-culture and other elements of the cellular microenvironment. The pathways of cell delivery are discussed with respect to specific clinical situations, including delivery of ex vivo manipulated cells via local and systemic routes, as well as activation and migration of endogenous reservoirs of reparative cells. The volume concludes with an in-depth discussion of the tracking of cells in vivo and their various regenerative activities inside the body, including differentiation, new tissue formation and actions on other cells by direct cell-to-cell communication and by secretion of biomolecules."